The study was then run during the workweek so as to provide a high-workload environment

When humans lose weight, either in outer space or on Earth, this weight is in the form of both lean body mass and fat mass . In non-astronaut populations, the goal of weight loss is usually to lose more fat mass than lean body mass. Indeed, when healthy, ambulatory humans lose weight on Earth, most of this weight is in the form of fat mass, with a lesser percentage of the lost weight coming from lean body mass . However, when humans are not ambulatory, as is the case with astronauts during transport, a larger percentage of the lost weight can come from lean body mass. In one crossover study – a type of study in which the same participants are exposed to all conditions – Biolo and colleagues tested the consequences of a weight-loss diet versus a weight-maintenance diet during either ambulatory or non-ambulatory conditions. When participants were on the weight-loss diet and ambulatory, most of their weight loss was in the form of lost fat mass rather than lean body mass . However, when participants were on the weight-loss diet and bed rest, their weight loss was in the form of similar amounts of lost fat mass and lean body mass . In other words, weight loss coupled with inactivity leads to greater loss of lean body mass. The loss of lean body mass is already a phenomenon that occurs in human and nonhuman animals living in micro-gravity . Therefore, weight loss could exacerbate this loss of lean body mass in astronauts, which could lead to the loss of muscle volume and the loss of bone mineral content . These outcomes could lead to increased risk for soft tissue injury , bone fracture, and decreased stamina , which could increase astronauts’ risk of being injured during extravehicular activities and of having difficulty readjusting to gravity on Earth or other planets. In summary,vertical agriculture when astronauts are in a micro-gravity environment, and especially when they are physically inactive, such as they will be in the Crew Transportation Vehicle, weight loss could result in the loss of lean body mass.

Consequently, assessing the impact of space food on weight loss will be important. Sleep difficulties are also common in astronauts. Astronauts sleep significantly less during ISS missions, as compared to after, and 75% of ISS crew members report using medications to promote sleep . The most frequently used sleep medication during spaceflight is zolpidem , a medication with side effects that can include difficulty with balance, unusual dreams, headache, gastrointestinal problems, and feeling “drugged” . Despite the common use of this and other sleep-promoting medications among astronauts, and despite a NASA mandate that astronauts have 8.5 hours for sleep per night, ISS astronauts average only 6.09 hours of sleep a night . Sleeping 6 to 6.9 hours a night was shown in one epidemiological study of over 175,000 people to significantly increase the risk for work-related injury . Sleep deprivation has also been linked to psychological impairments such as negatively biased mood, difficulty using one’s emotions to make decisions, impaired frustration tolerance, and reduced attention, vigilance, and memory . Even when alertness is restored with stimulants such as caffeine, many of these impairments remain . Astronauts have access to coffee, caffeine pills, and stimulant pills, such as modafinil . Yet their journals still report numerous instances of sleep deprivation leading to impaired functioning, such as “I fell asleep while typing” and “The fatigue was evident when a couple of minor mistakes were made today on some payload activities . . . it is an obvious indicator of fatigue” . Astronauts’ sleep deprivation could pose a serious threat to both themselves and to the success of space missions . Factors that can exacerbate sleep difficulties should therefore be avoided . Food is one such factor that could exacerbate sleep difficulties. In a nationally representative study of 5,587 U.S. adults, eating a reduced-variety diet, consuming less salt, and consuming a low number of calories was associated with self-reports of sleeping less than five hours a night, as compared to self-reports of sleeping 7 to 8 hours a night . The researchers also found significant associations between sleep duration and the intake of numerous nutrients, including intake of carbohydrates, proteins, vitamins, and minerals . In summary, aspects of food intake have been associated with impaired sleep, and because astronauts already have sleep difficulties, it is important to evaluate how new space food diets impact sleep.

Unlike sleep difficulties and weight loss, poor self-reported health is not often emphasized by NASA as a potential health risk. However, asking participants to rate their own health as excellent, very good, good, fair, or poor is well recognized in health fields as a robust, reliable, and valid way to assess overall health status . Self-reported health, also called self-rated health or perceived health, predicts functional ability and mortality . Self-reported health predicts mortality even after controlling for numerous potential confounds such as age, sex, income, education, and health practices . Asking participants to rate their own health is a robust predictor of health outcomes, even when the wording of the question varies . Self-reported health is usually used as an indicator of health over long time periods, but researchers have found that participants’ ratings can also change over relatively short periods of time, indicating that self-reported health could be used as a marker of short-term changes in health. For instance, when 9,235 participants in the 2005-2008 National Health and Nutrition Examination Survey were surveyed at two time points one month apart, nearly 40% of participants changed their response to the question, “In general, would you say your health is excellent, very good, good, fair, or poor?” . Additionally, when a variant of the self-reported health question, “Overall, how satisfied were you with your health today?” was used in a 56-day survey study, researchers found significant day-to-day, within person variability . Greater day-to-day health satisfaction was also associated with fewer health events . Consequently, although self reported health is traditionally used as an indicator of health over long time periods, it can likely also be used to assess variation in self-reported health over days or weeks. Self-reported health could therefore be used to assess how new space food diets impact health over time.To ensure participants were representative of future commercial astronauts, all participants had to express an interest in traveling to outer space. Participants also had to be willing and able to eat breakfast, lunch, and dinner at work Monday through Thursday for two weeks. Additionally, participants had to be willing and able to eat only the food provided during the experimental condition and to eat from a restricted number of food venues at the workplace during the control condition. These eligibility requirements were anticipated to increase study adherence. Participants also had to report no endocrine or metabolic disorder, as eating the processed, ready-to-eat food could have exacerbated these disorders. Finally, participants had to report no current dieting and no history of an eating disorder, as these factors could have adversely impacted participants’ eating or rating of the foods. UCLA Institutional Review Board approval was obtained prior to conducting study procedures.

A parallel crossover design was used over the course of two weeks. The parallel crossover design was selected because this type of design achieves greater statistical power and precision with fewer participants, as compared to a parallel design , and recruiting participants from the pool of commercial aerospace employees was anticipated to be difficult. For the parallel crossover design to be most effective, a “washout” period between conditions is required . Therefore, this study involved food manipulation Monday through Thursday with a three-day “washout” period Friday through Sunday. During this washout period, participants ate as normal without recording their food intake. During week 1, half the participants were randomly assigned to the experimental condition, while the other half were in the control condition. During week 2, this arrangement flipped,vertical farming aeroponics with the participants who were previously in the experimental condition switching to the control condition, and vice versa. Both the experimental and control conditions lasted 4 days in Week 1 and 4 days in Week 2 . All participants completed the study during the same two-week period. The procedure is shown in Table 3. Each week of the study required approximately 107 minutes of the participant’s time. Participants also completed a brief qualitative assessment at the very end of the study, which took approximately 10 minutes. This brought a participant’s total time commitment to 224 minutes, or approximately 3.75 hours, for the entire study.Regardless of the condition to which they were assigned, participants met me in a workplace conference room between 8:00am and 10:00am on Monday morning. At that time, they received their condition instructions , along with a bullet-point list of foods they could and could not week eat that week. All participants were reminded they would be weighed right then and on Friday morning, before eating. They were also reminded they would receive an email with a link to an online survey at 5:00pm on Monday, Tuesday, Wednesday, and Thursday of both weeks. Finally, all participants were told they would receive text message reminders to complete the survey at 6:00pm and 7:00pm each night, and they were expected to complete the survey before 8:00pm. Participants were asked to complete the survey on a computer, rather than on a smartphone, so that all questions would display in correct formatting. The time frame of 5:00 to 8:00pm was chosen for the evening survey because participants often remained at work until 7:00pm or later, and I expected participants would be more likely to complete the survey if they completed it before leaving work. However, data were not discarded for being submitted after 8:00pm.When participants met me on Monday morning, they received their tote of experimental condition food. The tote included four gallon-sized plastic bags, with each bag containing one day’s worth of food. The bags were labeled Day 1, Day 2, Day 3, and Day 4. Each gallon-sized bag contained four smaller plastic bags in which the food was actually stored. These bags were labeled Breakfast, Lunch, Dinner, and Snack. Participants were also provided with a binder that showed the breakfast, lunch, dinner, and snack options that were provided for each day. Participants were informed that the meal categories were recommendations only and that they could eat anything from the tote at any time. Because the food was designed to be lightweight and portable, participants were able to carry the tote with them everywhere they went. All totes contained the same exact food . This food was designed to provide sufficient calories for all participants. All totes also included eight empty two-gallon-sized plastic zip bags for storing leftover food. When participants met me on Monday morning, they received vouchers for four days of meals at work, the control condition instructions , and four Food Rating Logs . The control condition instructions outlined that, for the next four days, they would be allowed to eat from the workplace food outlets that served restaurant-style, pre-determined portions . This provided participants with approximately 12 meal options at any time of the day. Participants were not allowed to eat from the cafeteria-style line at work, nor were they allowed to eat from the graband-go venue, with the exception of the yogurt, milk, and cereal that was served at that venue. Participants were also not allowed to eat from the frozen yogurt stand or from the specialty coffee stand. Restricting participants from these foods had the benefit of allowing me to more accurately estimate their nutritional intake and to provide the experience of seeing food yet being unable to eat it. This experience, of seeing food and being unable to eat it, will not occur in outer space. Therefore, providing this experience in both the experimental and control conditions provided feelings of deprivation in both conditions, thereby effectively eliminating this deprivation from being a cause of different responses to the two conditions. Prior to starting the study, participants completed a Work-Specific Food Survey . This measure was used to screen participants and to provide descriptive information on the sample. This measure was not used as a moderator in any analyses. On Friday, participants also completed the Ten-Item Personality Inventory . This measure was also used to provide descriptive information on the sample and was not used as a moderator in any analyses.

Similar inhibition was observed when 2-heptanone was applied alone or coapplied with eucalyptol

In a laboratory setting, chlorantraniliprole was harmless to Orius laevigatusfor residues aged 1-14 d, in contrast to abamectin, which resulted in nearly 100% mortality up to 14 d . In a field setting, the half-life of chlorantraniliprole on rice straw was 3.5 d , and in sugarcane, was 8 d at both 1x and 2x the recommended field rate . Hence, the relatively short half-life of chlorantraniliprole compared to that of lambdacyhalothrin, further suggests that it had minimal effect on the acute mortality of H. convergens mortality in our study, which was still substantial by day 8 . The persistence of the toxicity effects of pyrethroid residues in the field appears to vary considerably among natural enemy species and active ingredients. For example, field-aged residues of esfenvalerate remained highly toxic to adult Trichogramma platneri Nagarkatti after 21 days, but were harmless after 7 days for Colpoclypeus florus. In addition, residues of permethrin and esfenvalerate on almond twigs were sufficient to cause 50% acute mortality of G. occidentalis even after 7 months of aging in the field . Nonetheless, pyrethroids are subject to photodegradation under field conditions. When exposed to UV light, lambda-cyhalothrin can degrade to 5% of the initial amount applied after 20 min . Similarly, when applied to a rice paddy, the half-lives of both components of the combination insecticide were determined to be 5 days . Thus rates of degradation of lambda-cyhalothrin under field conditions may vary with formulation, UV exposure within the canopy of the crop, and with residue substrate. Despite the potential for degradation of lambda-cyhalothrin under field conditions, the high level of sensitivity of the voltage-gated sodium channels of insects to disruption by pyrethroids resulted in the persistence of acute effects on H. convergens larvae in a walnut orchard after 38 days. From this study we have been able to show that acute mortality response of H. convergens to the insecticide combination of chlorantraniliprole and lambda-cyhalothrin was affected by residue age, setting, and life stage.

Adults and larvae both experienced high levels mortality when exposed to fresh residues of the combination insecticide. Chlorantraniliprole is frequently not toxic, whereas lambda-cyhalothrin is highly toxic,low round pots to a number of natural enemy species, and therefore the latter active ingredient was likely responsible for the high mortality of H. convergens. Larvae were more susceptible to the insecticide residues than adults, and aging had a greater effect for field-aged residues that were exposed to UV from natural daylight than for laboratory-aged residues that were exposed to fluorescent lighting. Thus, traditional laboratory bio-assays can yield greater estimates of the persistence of acute mortality responses among natural enemies than bio-assays based on field-aged residues. However, the acute mortality responses of H. convergens to fresh residues of the combination insecticide were similar for insects exposed to field-aged or laboratory-aged residues. This indicates that traditional laboratory bio-assays remain a useful tool for assessing acute toxicity for fresh residues, while bio-assays with field-aged residues are needed to accurately assess the persistence of toxic effects on natural enemy mortality. Integration of chemical signals at the peripheral sensory system remains one of the least understood mechanisms of insect olfaction, particularly in mosquitoes. Despite the great progress made in the last 2 decades in understanding how receptors form the basis of chemosensory perception in insects, how olfactory signals integrate at the periphery remains an enigma . ‘‘It is as if a new continent has been discovered but only the coastline has been mapped’’ . In the largest majority of reported cases , antennal neurons of Cx. quinquefasciatus displayed excitatory responses , but evidence for inhibitory responses , already known for Ae. aegypti , is now emerging for Cx. quinquefasciatus . It has been observed in moths , beetles , the fruit fly , and mosquitoes that activation of one neuron interferes with signaling of other olfactory receptor neurons . It has also been reported that a single compound caused reduction of nerve impulse followed by a transient post-stimulus excitation . Although Carlson and collaborators elegantly demonstrated that in the fruit fly lateral inhibition is most likely mediated by ephaptic coupling , the complete ensemble of the molecular mechanism of inhibition at the peripheral olfactory system of mosquitoes remains terra incognita.

A simple explanation of the ephaptic coupling is that, upon stimulation of an ORN, the potential declines. Consequently, per channel current generated by a cocompart mentalized neuron is reduced . This scenario argues that the firing of a neuron causes reduced spike frequency by a colocated neuron because of the close apposition of their neuronal processes. Although ephaptic coupling could explain lateral inhibition, other mechanisms of intraneuron inhibition may exist. While de-orphanizing odorant receptors expressed predominantly in Cx. quinquefasciatus female antennae, we serendipitously recorded currents from an OR that generate inhibition in response to certain odorants. Further studies unraveled a hitherto unknown mechanism of peripheral, intrareceptor inhibition in mosquito olfaction.To test whether the inhibitory responses were manifested in vivo at the periphery of the olfactory system, we generated transgenic flies, with CquiOR32 expression driven by DmelOrco promoter, and recorded electroantennogram responses by using a standard method . Not surprisingly, control flies gave strong response to -2-hexenal and weak response to methyl salicylate , whereas Orco-Gal4/UAS-CqOR32 flies gave robust response to methyl salicylate, with the strong response to -2-hexenal unchanged . w1118 flies gave very weak responses to eucalyptol at high doses, but interestingly Orco-Gal4/UAS-CqOR32 flies generated dose-dependent, inverse EAG responses . To further scrutinize this unusual reverse EAG responses, we used gas chromatography with electroantennographic detection . In GC-EAD analyses, injected mixtures are separated by GC and subjected to antennal preparations under the same condition thus ruling out any possibility of mechanical interference and minor sample contamination. Here, methyl salicylate responded with regular EAG responses, i.e., with the first phase , which is referred to as rise of the receptor potential, and the second phase starting at the end of the stimulus, commonly referred to as the decline of the receptor potential . This is analogous to the depolarization, repolarization, and hyperpolarization of a nervous impulse. As opposed to methyl salicylate, eucalyptol consistently gave inverse EAD responses thus corroborating what we observed in EAG analyses . Next, we recorded EAG responses when flies were challenged with odorants and an inhibitor. First, we compared the response of w1118 and Orco-Gal4/UAS-CqOR32 flies to -2-hexenal when it was delivered alone or in combination with eucalyptol. EAG responses from w1118 flies to 0.1% -2-hexenal alone or in combination with 10% eucalyptol did not differ significantly . By contrast, EAG responses from Orco-Gal4/UAS-CqOR32 flies to 0.1% -2-hexenal plus 10% eucalyptol were significantly lower than those elicited by 0.1% -2-hexenal alone . We then examined the dose-dependent effect of this inhibition by using Orco-Gal4/UAS-CqOR32 flies. Robust responses to 0.1% methyl salicylate were reduced in a dose-dependent manner with the addition of eucalyptol but remained unchanged at the end of the tests. Likewise, EAG responses to 0.01% -2-hexenal were reduced when coapplied with eucalyptol . Of note, -2-hexenal does not activate CquiOR32 .

Such inhibition presumably results from CquiOR32 indirectly inhibiting responses of the fly endogenous receptors to -2-hexenal. In these continuous experiments, a small difference between EAG responses before and after costimulus tests may be due to loss of this volatile semiochemical from the cartridge rather than adaptation. Taken together, these results further suggest that intrareceptor inhibition occurs in vivo as indicated by the inhibitory effect of eucalyptol on methyl salicylate responses. Additionally, the effect of eucalyptol on the response to -2-hexenal suggests that intraneuronal inhibition occurred. A few lines of evidence support this hypothesis. First and foremost,plastic pots 30 liters eucalyptol does not cause inhibition in control flies and -2-hexenal does not activate CquiOR32 . The simplest explanation is that, in Orco-Gal4/UAS-CqOR32 flies, all endogenous receptors are coexpressed with CquiOR32. Thus, CquiOR32 response to eucalyptol interferes with the response of DmelOR7a to -2-hexenal. In short, inhibitor and agonist are likely to be acting on different receptors in the same neurons, thus an intraneuron inhibition. To further test the notion of intraneuronal inhibition, we turned to single sensillum recordings .The best ligand for ab4A, the neuron in ab4 sensilla with a large spike amplitude, is -2-hexenal , although ab4A is also very sensitive to other ligands, including hexanal . Contrary to ab4B, ab4A houses only one OR, namely, DmelOr7a . Because expression of CquiOR32 was driven by DmelOrco, ab4A neurons in our transgenic flies house both DmelOr7a and CquiOR32. Coexpression was confirmed by a significantly stronger response to methyl salicylate recorded from Orco-Gal4/UAS-CquiOR32 than from WT flies , while retaining response to hexanal . It is known that methyl salicylate is the best ligand for DmelOr10a in ab1D but elicits only very low response in ab4A . The low response of WT flies to methyl salicylate did not differ significantly when the odorant was delivered alone or codelivered with eucalyptol . By contrast, responses recorded from Orco-Gal4/UAS-CquiOR32 flies were significantly lower when the two stimuli were delivered simultaneously from two different cartridges . Next, we tested whether CquiOR32 response to eucalyptol would affect DmelOR7a response to a cognate ligand, hexanal. Responses of WT flies to hexanal did not differ significantly when comparing hexanal alone with hexanal plus eucalyptol . Recordings from ab4 sensilla in the Orco-Gal4/UAS-CquiOR32 flies showed a slight, albeit not significant, increase in response to hexanal. This is unlikely to be due to hexanal activation of CquiOR32 . When hexanal and eucalyptol were delivered simultaneously firing of DmelOR7a was completely abolished . We also recorded from ab7 sensilla, which expresses DmelOR98a, in ab7A and for which butyl acetate is one of the best ligands . Eucalyptol elicited inhibitory response in ab7A neurons of Orco-Gal4/UASCquiOR32 flies . In the transgenic flies both methyl salicylate and butyl acetate generated excitatory responses , which were inhibited by eucalyptol . Because methyl salicylate and eucalyptol elicit inward and reverse currents in CquiOR32, this in vivo inhibition is not surprising. However, the consistent observation that eucalyptol inhibits the response of an endogenous receptor to a cognate ligand supports the notion that intraneuronal inhibition occurs when receptors are colocated in a neuron. Specifically, the inhibitory responses of CquiOR32 interferes with the activation of a collocated receptor by a cognate ligand.

For example, activation of DmelOR7a in ab4A neuron by hexanal and activation of DmelOR98a in ab7A neuron by butyl acetate were both inhibited by eucalyptol upon interaction with CquiOR32. Contrary to the fruit fly, which expresses only one receptor per neuron , mosquitoes can coexpress multiple ORs in the same neuron .Tissue fibrosis and cancer are two major causes of high human morbidity and mortality worldwide. Although there are multiple therapies for cancer, including chemotherapy, oncologic surgery, and radiation therapy, an effective therapeutic strategy is needed.1 Among these therapeutic strategies, chemotherapy is the main tool for curing various cancers. The therapeutic resistance of anticancer drugs, such as 5‐fluorouracil, gemcitabine, gefitinib, and trastuzumab, has been widely observed in the clinic.2 However, due to the lack of effective therapeutic drugs, tissue fibrosis still threatens human health. Although some drugs exhibit anti-fibrotic effects, including angiotensin‐ converting enzyme inhibitors, aldosterone inhibitors, statins, angiotensin II type 1 receptor blockers, endothelin receptors, β‐blockers, acetylsalicylic acid, and matrix metalloproteinase inhibitors, none of them are specifically designed to target fibrosis, and the related side effects limit their clinical use for treating fibrosis.Thus, anti-fibrotic and anticancer treatments are extremely urgent, and new therapeutic drugs should be designed based on specific targets that contribute to the progression of fibrosis and tumors. Epithelial‐mesenchymal transition is a reversible terminal differentiation process in which epithelial cells shed their properties and acquire a more mesenchymal phenotype.EMT is a fundamental process widely involved in the development and the progression of various diseases, and there are mainly three types of EMT. Type I EMT is involved in embryonic development and organ formation. Type II EMT is critical for wound healing and fibrosis. Type III EMT contributes to the progression and metastasis of tumors.Extensive studies revealed that EMT profoundly contributed to the production of myofibroblasts, which are the major cells producing massive amounts of collagen that leads to the deposition of collagen in the development of fibrosisIn addition, EMT confers increased motility and invasiveness in epithelial‐derived tumor cells and promotes tumor metastasis. Therefore, fibrosis and tumors share the common process of EMT, and drugs that specifically target EMT may exhibit both anti-fibrosis and antitumor effects, which will provide an effective strategy against fibrosis and tumors.

Fungicide effects on natural enemies are frequently focused on predatory mites

Copper hydroxide is the active ingredient in the pesticide marketed under the trade name Kocide 3000, and mancozeb is the active ingredient in the pesticide Manzate Pro-Stick. They are used to control both bacterial and fungal pathogens in numerous crops, including citrus, conifers, vegetables, tree crops, cereals, and small fruits. In high-value tree crops, they are used in combination to control pathogens such as apple scab, pear scab, fire blight, and powdery mildew . A mixture of copper hydroxide and mancozeb caused significantly high mortality in the predatory mite G. occidentalis, but at a concentration that was twice the maximum label rate. The same study found that, even at a diluted concentration, , exposing females to the pesticide mixture did not affect hatch rates, but, once hatched, the larvae had a higher mortality . On the other hand, a different predatory mite, Amblyseius cucumeris , appears to be compatible with copper hydroxide, in that exposure only causes high mortality at levels 10 times the recommended field rate. Copper hydroxide also had no significant effect on mortality or fecundity on the predatory mite Euseius victoriensis , whereas mancozeb significantly lowered mortality as well as fecundity, with no females laying eggs after treatment . With respect to parasitoids, copper hydroxide has shown little to no toxicity on the predator of citrus leafminer, Ageniaspis citricolaor Tamarixia radiata , a parasitoid of the Asian citrus psyllid . Mancozeb applications, suspected as the cause of low parasitism rates in Indonesian crops,hydroponic bucket demonstrated no toxicity to four different parasitoid species: Hemiptarsenus varicornis , Opius sp., Gronotoma micromorpha, and Diglyphus isaea.

These results suggest that the effects of copper hydroxide and mancozeb vary for different species, and their compatibility with natural enemies cannot be generalized. Lambda-cyhalothrin is a broad spectrum pyrethroid. One of its trade names is Warrior II, approved for use in a wide variety of crops, such as alfalfa, cereal crops, vegetables, tree nuts, tree fruits, cotton, and tobacco. In high-value tree crops, it is used to control many different pests: apple aphid, walnut aphid, codling moth, pear psylla, leafrollers, leafhoppers, and ants. This active ingredient is highly toxic to bees via direct application or residues on vegetation, and should not be applied when either crops or weeds are in bloom. Lambda-cyhalothrin is also highly toxic to aquatic organisms and wildlife, and areas subject to pesticide drift or runoff are considered hazardous . Lambda cyhalothrin has also demonstrated toxic effects on several natural enemies. The predatory mite, G. occidentalis, experienced 96% mortality at the full field rate. Even at 0.1x the full field rate, it was highly toxic to G. occidentalis, causing 76% mortality . In order to test for resistance, one study topically exposed 28 different populations of ladybird beetles to lambda cyhalothrin. However, the majority of populations tested displayed an LD50 below the maximum recommended field rate, including all populations of Coleomegilla maculata, Cycloneda sanguinea, Harmonia axyridis, and 6 of 8 H. convergens populations . Lamba-cyhalothrin is also toxic to both the larvae and adults of two green lacewing species, C. carnea and C. johnsoni . Additionally, it is highly toxic to the parasitoid, Diadegma insulare , which parasitizes diamondback moth, a major pest of brassica crops. Moreover, D. insulare can distinguish between host larvae fed on lambda-cyhalothrin treated plants versus non-treated plants, indicating a change in host preference .

Novaluron is an insect growth regulator, marketed under the trade name Rimon. It is approved for use in crops such as brassica, berries, potatoes, pome fruit, and stone fruit. In pear and apple orchards, it is used to control pear psylla, leafrollers, and codling moth. Its mode of action is to disrupt cuticle formation and deposition during molting. Although novaluron is not a conventional insecticide, it still may have non-target effects on beneficial insects, such as pollinators. For instance, exposure to novaluron may interfere with the development of honey bee larvae. Therefore, its application may not be compatible with beneficial insects when crops are in bloom. In addition, it has demonstrated toxicity to fish and aquatic organisms . Novaluron appears to have variable toxicity on several natural enemies. It demonstrated a low toxicity to O. insidiosus and Chrysoperla rufilabris , both of which are natural enemies in blueberry production . However, when exposed to novaluron residue aged 7 days, nearly 50% of H. convergens displayed acute effects, meaning they were either killed or knocked down. For G. occidentalis, an important predatory mite in apple orchards, novaluron is moderately toxic. Though it did not significantly reduce fertility, it caused reductions in fecundity as well as fertility . It has also demonstrated toxicity to green lacewing larvae, none of which survive to the adult life stage after treatment . Moreover, though it did not impact fecundity, it significantly reduced fertility and egg viability. Podisus maculiventris , a predator of the potato beetle, is susceptible through both direct contact and residual exposure . Additionally, when fed treated prey, 5th instar larvae were unable molt in to adults. Despite its impacts on survivor ship and reproduction, novaluron is still seen as a better alternative to pesticides with greater acute toxicity. For instance, when compared to brassica crops treated with broad spectrum pesticides , novaluron treated crops had higher yields and higher rates of parasitism in the pestiferous diamondback moth .

Spinetoram is chemical derived from the soil bacterium Saccharopolyspora spinosa. It is used as the active ingredient in an insecticide, marketed under the trade name Delegate, which is used to control foliage damaging pests such as leafminers, psyllids, and lepidopterous larvae. It is approved for use in a number of crops, including bananas and plantains, bushberries, hops, citrus, pome fruits, tree fruits, and tree nuts. In pome fruits, it is used to suppress populations of apple maggot, pear psylla, thrips, light brown apple moth and codling moth. In addition to targeting pests, spinetoram is toxic to bees exposed to treated crops, either though foraging on pollen-shedding or nectar producing plant parts. Delegate is recommended for use in integrated pest management programs and is advertised as being compatible with natural enemies, such as ladybird beetles, lacewings, assassin bugs, and spiders . Spinetoram has been demonstrated to be highly toxic to natural enemies and pollinators. For instance, T. triozae is a key parasitoid of the tomato psyllid, Bactericera cockerelli . T. triozae experiences 100% percent mortality when exposed to spinetoram via surface residue,stackable planters even when residue is aged as much as 15 days . Moreover, ingestion of spinetoram resulted in 100% mortality within a period of 12 hours. Additionally, spinetoram is highly toxic to eggs and larvae of the predatory mite G. occidentalis. It also caused 100% mortality in adult females after 72 h of exposure . Spinetoram is also toxic to pollinators via ingestion of treated sugar water, and it may cause mortality through exposure to either dry or wet residue. It is highly toxic to worker bees, and induces 100% mortality in bumble bees when applied at recommended field rates . Moreover, Neochrysocharis formosaand Ganaspidium nigrimanushave demonstrated susceptibility to spinetoram . These natural enemies are important parasitoids of Liriomyza trifolii , a major pest of vegetable and ornamental crops worldwide. Furthermore, spinetoram consistently lowers survival of both parasitoid species when exposed by direct application, residue, or ingestion. Sulfur is commonly used as both a fungicide and acaricide. Known as dry flowable sulfur or wettable sulfur, it is a dry powder that may be mixed with water and used as a foliar spray. It is the active ingredient in the pesticide marketed under the trade name Kumulus, which is used in an extensive variety of crops: ornamentals, turf, alfalfa, brassica, citrus, berries, cotton, hay, tree fruits, peanuts. In apple and pear orchards, sulfur is used to control plant pathogens, such as powdery mildew and scab, and pests, such as the two spotted mite and the red spider mite . It is also ranked as having variable impacts on natural enemies in tree fruits, ranging from low toxicity to aphid parasitoids to high toxicity on the western predatory mite, G. occidentalis . In apple orchards, G. occidentalis is a predator of tetranychid mites, such as the two spotted spider mite and the European red mite . Sulfur residue demonstrated a low toxicity to G. occidentalis adult females, and it had no effect on prey consumption. However, sulfur may have variable toxicity depending on the life stage of natural enemies, because the same study found that sulfur residue was highly toxic to larvae . It has also been shown to affect populations of another predatory mite, Iphiseiodes zuluagai , which preys on the coffee pest Oligonychus ilicis . The recommended field concentration caused approximately 60% mortality of I. zuluagai and decreased reproduction in adult females . Psyllobora vigintimaculatais a mycophagous coccinellid that may reduce the severity of the plant pathogen powdery mildew fungi. Additionally, sulfur was toxic when applied directly to P. vigintimaculata, resulting in 100% mortality within 24 h of exposure . Furthermore, when applied in commercial vineyards, sulfur reduced the density of P. vigintimaculata. Sulfur has also shown to affect multiple life stages of the predatory mired bug, D. brevis, causing acute toxicity in both nymphs and adults .

Exposure also decreased survival of nymphs to the adult life stage , fertility in adult females, and egg viability. Three main routes of exposure have been addressed in the literature: topical, residual, and oral. It is well known that natural enemy susceptibility to pesticide varies depending on exposure route . In a field setting, it is possible for natural enemies to be exposed to pesticide through all three aforementioned routes: topical exposure from direct spraying, residual exposure from a treated plant surface, and/or oral exposure from ingestion of a treated food source . Therefore, to more accurately assess the effects of pesticide exposure on natural enemies, it is necessary to examine multiple routes of exposure. There are several different methods for assessing the effects of pesticides on natural enemies . One route of exposure for assessing pesticide toxicity is to directly expose organisms via topical application. A common tool for topically applying pesticide is through the use of a Potter Spray Tower, which sprays a specific volume of the pesticide solution over a specified surface area . For instance, topical application via a Potter Spray Tower was used to assess the effects of buprofezin, an insect growth regulator that inhibits chitin synthesis, on several general predators, including H. axyridis, Stethorus punctum picipes , Orius tristicolor , Geocoris pallens, and Geocoris punctipes. In addition to direct spraying, there are other methods of topical application. For instance, to measure the effects of several conventional and biorational insecticides on the eggs of the generalist predator Chrysoperla externa , eggs were directly dipped into maximum field rate solutions for 25-s . While topical applications are a factor to consider when assessing pesticide risk, in a field setting, natural enemies are more likely to encounter pesticide via a combination of routes, including residual and oral exposure.Another approach is to measure pesticide toxicity via residual exposure, whereby a substrate is treated with a given pesticide, and the organism is then exposed to the treated substrate. For example, several pesticides frequently used in peach orchards were tested for their effects on the lacewing predator C. carnea using a Potter Spray Tower to apply residues to glass plates, and the predators were then exposed to the dried residue . Additionally, a Cornelis spray chamber was used to coat the sides of glass cages, to which the predatory stinkbug Picromerus bidenswas then added . Another study used a leaf dip bio-assay, in which pesticide residue was formed by dipping green bean leaves into pesticide solution for 5-s. In this manner, reduced-risk pesticides were then tested on multiple natural enemies: O. insidiosus, Amblyseius swirskii , and Eretmocerus eremicus. While most studies are based on fresh dried residues of pesticides, an equally important, but less commonly studied aspect of residues as a route of exposure for natural enemies is their persistence in the field . Several studies have begun to examine how the age of pesticide residue impacts natural enemies .

The shelter capability of artificial windbreaks is also influenced by their permeability

An accumulation of insect pest near windbreaks is more evident in windy weather as compared to calm weather conditions . Higher permeability of artificial windbreaks leads to higher wind speed in the leeward side, lower sheltering effects for insect pests, and lower insect pest density near the artificial windbreaks . Furthermore, higher windbreak permeability also shifts the positions of the highest insect pest density further away from the windbreak. Instead of maximal insect pest density at one wind break height for 0% permeable windbreak, the highest density was observed at distance equivalent to 2 to 3 windbreak height for thrips , aphids , fungus gnats , and gall midges . Besides artificial windbreaks, natural hedgerows also exert similar effects on insect pest distribution . In another experiment, using trace of rubidium element to mark egg parasitoids in the genus Aragus overwintering in French prune trees, Corbett and Rosenheim showed that the peak in Aragus density did not coincide with the original points of dispersal but some distance downwind, displaying certain degree of windbreak effect. Therefore, it can be inferred from these studies that the wake zone, which, in this case, can be considered as edge environment, traps insects along edges, resulting in their higher density along edges as compared to field interior.Several studies have examined effects of the combination of natural landscape fragmentation and microclimatic conditions and how such variables affect insect communities in non-agricultural habitats . The spatial distribution of a butterfly, Lopinga achine Scopoli ,hydroponic nft system showed distinct edge-biased distribution, which was explained by specific micro-climatic conditions leading to the ground cover of Carex montana L. having the highest abundance near forest edges .

In a study of bark beetle [Ips typographus L. ] infestations, Kautz et al. investigated the risk of infestation in three types of forest edges and compared the results of trees from the interior of the same forests. They concluded that the risk of bark beetle infestation was highest in forest patches cleared by sanitary logging measures, in particular along south-facing edges. Thus, the combination of a particular edge management practice and ambient temperature was highlighted as a key driver of bark beetle infestations. Although exclusively based on analyses of data derived from natural habitats, such studies strongly suggest that edge-biased distributions are often explained by micro-climatic differences between edge and interior locations. Using different types environmental sensors, it has been demonstrated how abiotic variables, including ground surface temperature and soil temperature, show considerable with-field variation and in particularly vary between edges and inwards into fields . Such micro-climatic variation can lead to spatial variation in crop growth and relative suitability of host plants and therefore lead to edge-biased distribution of herbivorous insects in agricultural systems.Although windbreaks and hedgerows are common features in many agricultural systems, sole reliance on the shelter effect and microclimate promoted by these features does not provide encompassing account for the occurrence of edge-biased distributions, especially for agricultural systems in which they are not present. Other factors that are more intrinsic to the agricultural environment, such as the nature of landscape matrix, have been shown to affect insect rate of dispersal and emigration and result in their aggregation along edges. In a marked release and re-captured experiment on movement of delphacid plant hopper, Prokelisia crocea Van Duzee , in patches of prairie cord grass, the rate of emigration from cord grass patches bordered with brome grass matrix was higher than that from cord grass patches bordered with mudflat .

The same study also noted the accumulation of plant hoppers along cord grass-mudflat edges, but no such aggregation of plant hoppers was observed along cord grass-brome edges. It was later confirmed that the lower permeability of cord grass-mudflat edges makes this type of edges a barrier to emigration since plant hoppers behaviorally avoid crossing highly contrast border between vegetated cord grass matrix to sparsely vegetated mudflat matrix . Moreover, the cord grass-mudflat border was clearly not a reflective edge, as plant hoppers did not show edge-avoidance behavior. Meanwhile, the distribution of plant hoppers within a homogenous patch of cord grass was found to be random . Therefore, although landscape matrix permeability may explain why insects can be contained in their original patches, it does not directly explain the aggregation of insects along edges, especially for the case of delphacid plant hoppers.In cases where agricultural systems are adjacent to natural forests, the edges can be described as an “ecotone” that marks the ecological change between two environments . The adjacency of vegetation of two different habitats results in an increase in floral diversity and vegetation heterogeneity . The increase in heterogeneity of vegetation along field edges has been shown to increase carabid species richness along field edges . For example, boreal forests with sparse ground vegetation were found to have lower numbers of herbivorous invertebrate prey for carabids . The interspersion between grasses, shrubs, and boreal trees as seen in the edges between farming lands and boreal forests can effectively increase the density of ground vegetation, resulting in greater abundance of herbivorous invertebrates which, in turn, leads to higher carabid abundance along edges . Similarly, the interspersion of vegetation types between the forest edges and urban habitat in north Ohio has been attributed to the increase in ant species richness .

Therefore, the ecotone environment observed along field edges could serve as a preferential habitat for some insect species.In the discussion of edge-biased distributions in relation to the vegetation heterogeneity, there seems to be an underlying assumption that vegetation homogeneity exists within a given habitat or agricultural system. Therefore, the heterogeneity of vegetation observed in the ecotone along edges is mainly caused by the interspersion between the vegetation types of two environments, while the within-system variation of vegetation is often ignored. However, despite cropping systems predominantly being monocultures and under a quasihomogeneous management regime, there is broad evidence of significant vegetational heterogeneity within agricultural fields. That means individual crop plants within an agricultural field may have differential growth rates, phenotypes, and quality. This issue was highlighted above as microclimatic conditions may vary within fields and show distinct gradients between edges and locations further inwards into fields . Edge-biased crop development has been observed and reported for almost 100 years in winter wheat fields,nft channel where wheat rows along the borders showed higher yields than those in the center . Over the years, rice , maize and climbing beans , wheat , millets, Sudan grass , soybean , cotton , rapeseed , carrots, cabbages, and onions have been shown to display edge-biased distribution of growth. In rice, the increase in yield of border rows compared to central portions of fields or plots ranged from 63 to 68% . The difference can be as large as 394% between edge and center crops . The major factors accounting for such edge-biased growth difference have been attributed to competition for nutrients and light among crop plants . The body of research documenting edge-biased distributions of crop development often regards the phenomenon as undesirable and seeks ways to curb the effect to avoid overestimation in yield calculations . However, from an entomological perspective, the research focus would be to study how within field vegetational heterogeneity contributes to the edge-biased distribution of insects in agricultural systems. We are unaware of any published study addressing this question directly, but the edge resource model by Ries and Sisk could partially explain this, as micro-climatic conditions near edges may affect host plant growth and quality . Nonetheless, given that edge crops can have significantly higher yield than center crops, it is reasonable to hypothesize that there are physiological, and therefore nutritional, differences between edge and center crops. If such physiological differences are linked to differences in suitability as hosts and insects are able to—via volatiles or visual cues—perceive such differences among crop plants, then vegetational heterogeneity may partially explain observed edge-biased distributions of insects. That is, vegetational heterogeneity may drive selection by favoring both behavioral attraction and oviposition behavior by insects to certain plants. In addition, difference in suitability of crop plants will likely lead to differential growth and survival rates of insects.

As an example, longevity and fecundity of Sitobion avenae and Rhopalosiphum padi L. have been shown to increase with the level of nitrogen fertilizer applied to wheat host plants . Meanwhile, poor-quality host plants can cause many female insects to resorb their own eggs to mobilize nutrients for their survival . In broader term, female insects have been shown to vary their oviposition and number of eggs laid in accordance to the suitability of host plants for the performance of future progeny . Therefore, the better-quality edge crops may be preferred by insects or provide better growing conditions for insects and their larval stages, resulting in a skewed distribution towards crop edges. However, using plant vigor to explain edge-biased distribution of insects may also involve important trade-offs. On one hand, more vigorous plants may provide insects and their larvae with more nutrients for their development. On the other hand, healthier plants can also produce more defensive chemicals such as alkaloids, glucosinolates, and phenolics to protect themselves from insect herbivores . Furthermore, the idea of plant quality as potential explanation for insect aggregation along edges is also contested by the data reported by Haynes and Cronin . Their study found that the nitrogen content of plants along mudflat-cord grass edges and bromecord grass edges was both higher than that of plants in the interior. Interestingly, delphacid plant hoppers aggregated along mudflat-cord grass edges but not along bromecord grass edges, implying that host plant quality may not be the main driving factor of edge effect. Thus, we argue that considerable research is needed to investigate the complex of factors affecting plant growth along edges compared to inwards into cropping systems and how differential plant growth may affect their role as suitable hosts for associated insect communities.Originally, skewed distributions of agricultural insects towards field edges were mostly regarded as a source of error when developing insect sampling plans. Therefore, the data collected along field edges were not considered representative of the actual insect population . However, edge-biased distributions of insects in agricultural systems can potentially provide opportunities to optimize sampling efforts. Currently, sampling units employed in sampling plans are often randomized and spread across the field. Such an approach can be highly labor intensive. Given the prevalence of edge effects in many insect species, stratified sampling plans with a greater focus along field edges than field interiors can reduce sampling efforts as well as increase sampling accuracy if a stable spatial pattern of insect distribution within an agricultural system is well studied and established. For example, increased performance of such a spatially targeted sampling approach was demonstrated for the wheat stem sawfly . In addition, Severtson et al. described a spatially optimized sequential sampling plan for cabbage aphids in canola fields. In their study, canola fields were divided into two types of sampling grids: inner grids and edge grids. Edge grids were defined as the areas within 20 m of the field edge, while inner grids were the rest of the sampling grids. Their sampling results showed that 9 out of 20 edge grids displayed infestation level above threshold while only 2 out of 20 inner grids showed infestation level above threshold. Taking the proposed edge effect distribution of aphids into account, Severtson et al. conducted stratified sampling analysis and managed to reduce spatial variability as well as to increase accuracy of infestation level. Nonetheless, we also acknowledge that edge effect distribution of insects in many agricultural systems can be highly seasonal and temporally dependent .Furthermore, applications of insecticides in agricultural fields have been proven to greatly change the edge-biased distribution of insects to random distribution across agricultural fields . Therefore, the mentioned limitations may jeopardize the robustness of edge-stratified sampling methods and highlight the importance of timing in proposed edge-stratified sampling methods. Broadly speaking, increased understanding of the mechanisms responsible for edge-biased distributions can be used to improve the practices of precision agriculture. As compared to conventional agriculture, precision agriculture focuses more on timely and targeted application of treatments to control insect pest infestations rather than field-wide and calendar-based spraying of chemicals . The knowledge of edge-biased distributions can help create targeted sampling plans to generate more reliable mapping of insect distributions and enable more targeted application of pesticides used in IPM programs .

Metabolic dysfunction is an important aspect of the pathogenesis of several neurological diseases

The non-absorbed fructose can be rapidly propelled into the colon, where its contact with the anaerobic flora causes fermentation, bloating and diarrhea. It is remarkable that this action of dietary fructose on intestinal microbes can generate byproducts that influence systemic physiology and brain. Fructose entering the enterocyte cytosol may be phosphorylated by Ketohexokinase enzyme resulting in rapid depletion of ATP and accumulation of pyruvate and acetyl-CoA. Although these events help maintain the downhill fructose gradient into the cytosol, they also reduce intestinal Ca2+ and inorganic phosphate transport that compromises absorption of certain minerals essential for bone health. Under normal conditions, systemic fructose concentration is relatively low in healthy humans and tissues such that liver and kidneys are sensitive to small changes in circulating fructose. Excessive fructose intake also stimulates endogenous glucose production and lipid synthesis in the liver, events associated with the spectrum of MetS, such as obesity and systemic inflammation. Regarding fructose metabolism in intestine, the enteroendocrine cells after detecting fructose in the gut, activate a cascade of endocrine events. In particular, luminal fructose stimulates secretion of human PYY, cholecystokinin, neurotensin, and serotonin by secretory intestinal cells. A large body of literature indicates that most fructose is metabolized in the liver after being absorbed by the intestine to the bloodstream . The liver is the primary organ for processing lipids and proteins, which are exported to brain and other tissues and organs. Lipids are essential for brain function and behavior, being part of plasma membranes,stackable planters working as molecular transport systems, neuronal signaling systems, etc.. The brain contains the second highest concentration of lipids in the human body. The metabolism of brain lipids is tightly regulated through a liver-brain interaction in which the autonomic nervous system plays a crucial role.

Liver dysfunction can be aggravated by consumption of fructose as fructose is mainly metabolized in the liver where is converted into fatty acids that can reach the brain and expand the inflammatory reaction started in the periphery. Fructose is metabolized in liver via fructolysis, and the primary metabolites and by-products include glucose, lactate, triglyceride, free fatty acid, uric acid and methylglyoxal. GLUT5 is widely expressed in adipose tissue, kidney, muscle skeletal tissue, testis and brain that could also participate in fructose metabolism. It can be noted that fructose metabolism differs from that of glucose since hepatic fructose is converted rapidly to triose-phosphate independently of insulin control and without a citrate feedback. A large portion of fructose is converted into glucose which can be released into the bloodstream or stored as glycogen. Another portion of fructose is converted into fatty acids, which under exacerbation can contribute to the formation of hypertriglyceridemia and fatty liver disease. Furthermore, experimental long-term fructose consumption decreases mitochondrial enzymes that catalyze β-oxidation in the liver. Excessive lipid accumulation elicited by fructose in hepatocytes can also disrupt mitochondrial function and elevate levels of oxidative stress and inflammation. When compared with glucose, fructose over consumption exerts divergent effects on hepatic mitochondrial function. Quantitative electron microscopy revealed that fructose but not glucose increases the number of mitochondria in the liver, and increases fission and/or decreases fusion. These experimental data indicate that fructose-induced mitochondrial dysfunction may contribute to the development of fatty liver disease. Fructose consumption also induces pancreatic β-cells hyper-responsivity to glucosestimulated insulin secretion which can affect peripheral metabolism given the extreme sensitivity of adipose and other tissues to the action of insulin. The enzyme fructokinase C that rapidly phosphorylates fructose in the liver, reduces ATP, activates purine nucleotide turnover that culminates in the formation of uric acid as well as Reactive Oxygen Species and mitochondrial dysfunction.

Uric acid is a waste product from the breakdown of purines in the liver that once released to the circulation can reach the brain. Fructose catabolism in liver induces rapidly ATP depletion and release of uric acid to the systemic circulation resulting in hyperuricemia. In situations of high fructose consumption, oxidative stress promoted by accumulation of uric acid triggers an inflammatory response in liver and extrahepatic tissues, causing inflammation and lipid accumulation. Uric acid can harm the brain as seen in patients with Alzheimer’s and Parkinson’s disease in which uric acid acts as a risk factor for disease progression and a possible marker of cognitive dysfunction. The uric acid-mediated oxidative stress-induced lipid peroxidation causes DNA damage and activates inflammatory factors that lead to cell damage. The gut is the largest microbial, endocrine, and immune organ in humans and mice. The bacterial composition of the gut has emerged as profound regulator of whole-body metabolism and contributing to host immune homeostasis, and influencing brain function and disease. Gut microbiota plays an important role in brain-gut interaction and behavior by producing metabolites, hormones and immune factors that can influence the brain. Fructose affects microbiota composition and abundance that associate with metabolic dysregulation and select pro-inflammatory phenotypes in hypothalamus, liver and adipose tissue. Proinflammatory microbiota and its byproducts such as LPS recruit macrophages that bind toll-like receptors leading to the release of cytokines causing inflammation of the intestinal mucosa. As a consequence, there is a decrease in tight junction proteins resulting in a greater permeability of the intestinal barrier increasing the penetration of pathogens into the bloodstream. The hypothalamus is the master center for regulation of brain and body metabolism and control of appetite and feeding behavior, and works with the hippocampus to regulate cognitive function. The hypothalamus controls all body organs via the pituitary endocrine axis and the autonomic nervous system.

Fructose affects food intake by stimulating release of glucocorticoid hormones which feedback on the hypothalamus. Fructose over consumption , reduces total protein kinase B , Ser473-phosphorylated Akt , and insulin receptor phosphorylation in the hypothalamus. Insulin inhibits the expression of neuropeptide Y and agouti-related protein , which are orexigenic neuropeptides that stimulate food intake in the hypothalamus. Therefore, excess of circulating insulin secondary to fructose-induced insulin resistance dysregulates energy homeostasis leading to AgRP/NPY over expression, in association with an increase in appetite and body weight. Fructose affects appetite hormones like ghrelin, leptin and peptide YY , which are secreted in the periphery and travel via circulation to the hypothalamus. Fructose stimulates release of leptin from adipocytes and promotes leptin resistance together with an enhancement of satiety signals in the hypothalamu. Leptin resistance involves Janus Kinase -mediated phosphorylation, activation of transcription 3 functions, and impairment of leptin transport through the BBB. The leptin resistance elicited by high fructose , can occur on the absence of body weight gain or circulating leptin levels; therefore, it is possible that leptin resistance is an early feature in the chronic process of development of a fructose-induced metabolic disorder. On the other hand, a short period of fructose consumption in humans has been shown to result in lower levels of circulating insulin and leptin, and fails to suppress post-meal ghrelin levels. Therefore, it seems that the length and concentration of fructose intake are crucial determinants for the type of physiological response. It is notable the strong interaction between pathways that regulate food reward and metabolism in the brain, and that they become dysfunctional in metabolic disorders such as obesity. The hypothalamus harbors neurons that express the endocannabinoid receptor 1. The endocannabinoid system seems to play a regulatory role on the rewarding aspect of the consumption of palatable foods,stacking pots and particularly high fructose. Endocannabinoids levels are increased in response to fasting and are suppressed postprandially. In addition, a single intravenous injection of leptin, which regulates energy balance and eliminates hunger, reduces endocannabinoid release from the hypothalamus. Experimental evidence indicates that short-term consumption of fructose but not glucose increases mRNA levels of CB1 receptor and affects enzymes involved in the synthesis/degradation of endocannabinoids. The hypothalamus plays a crucial role on the control of brain and body homeostasis. Fructose has several metabolic effects in the hypothalamus such as depletion of ATP, increase in activation of AMP kinase, inactivation of acetyl-CoA carboxylase, reduction of malonyl-CoA, together with stimulation of food intake. Furthermore, fructose-induced hypothalamic AMPK activation increases hepatic gluconeogenesis by the elevation of circulating corticosterone level, further contributing to systemic insulin resistance. Fructose but not glucose has been shown to reduce hypothalamic cerebral blood flow in healthy volunteers . Ancillary, fructose is metabolized faster than glucose in the brain, pointing out another difference between fructose and glucose.

Fructose consumption can elicit robust changes in oxidative stress in the hypothalamus. For example, high-fructose consumption for 10 weeks decreases levels of antioxidant enzymes, including cytoplasmic copper-zinc superoxide dismutase 1, mitochondrial manganese superoxide dismutase 2, glutathione peroxidase, glutathione reductase, and catalase. The actions of fructose on hypothalamic metabolism may be operational for regulation of metabolic disorders such as obesity, insulin resistance , and other disorder. Using systems nutrigenomics in a rodent model of high fructose consumption, it has been reported that fructose uses the extracellular matrix biglycan gene to alter molecular pathways related to oxidative phosphorylation, glucose metabolism and fatty acid metabolism in the hypothalamus. This prominent response of Bgn in hypothalamus elicited by fructose is crucial to understand how metabolic disorders influence brain centers. The hippocampus plays a preponderant role on learning and memory processing and works with the hypothalamus to integrate feeding behavior with higher order functions. The hippocampus is highly susceptible to the action of fructose such that high fructose consumption results in alterations in cognitive function. Experimental evidence in rodents shows that over consumption of fructose for a duration , sufficient to disrupt peripheral metabolism reduces hippo campal insulin receptor signaling, which is commensurable to poor learning and memory performance. In addition, 15% fructose by 8 weeks compromises the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation and long-term depression , followed by reduction of synaptic contact zones and neurogenesis. Even a shorter period of fructose or sucrose consumption but not glucose, reduces hippocampal neurogenesis. Fructose consumption is currently perceived as an important cause of metabolic disorders with subsequent detriment of cognitive function. In this context, several mechanisms have been suggested for the action of fructose on cognitive function such as disruption in oxidative metabolism, decreases in neurotrophic factor expression, increases in oxidative stress and inflammation. A comprehensive study showed that high fructose consumption in rodents for 6 weeks disrupts pathways associated with cell energy metabolism involving peroxisome proliferation-activated receptor gamma coactivator 1-alpha , mitochondrial transcription factor A and sirtuin 1, and synaptic plasticity modulators such as cAMP response element-binding protein . The fact that PGC-1α interacts with TFAM on mitochondrial bio-genesis and SIRT-1 affects synaptic plasticity via post transcriptional regulation of CREB suggests that fructose may disrupt the interface between cell metabolism and synaptic plasticity, making the brain susceptible to neurological disorders. Interestingly, the effects of fructose on cognition may also involve inflammatory pathways that are affected by hepatic metabolism. For example, translocation of high mobility group box 1 , a highly conserved non-histone DNA-binding protein, from nucleus to cytoplasm in response to high fructose consumption elicits an inflammatory cascade involving Toll like receptor 4 , nuclear factor-kappa B and the transcription of proinflammatory cytokines. The TLR4/NF-κB signaling pathway activation elicited by HMGB1 induces apoptosis in hippo campal cells and subsequent cognitive deficits in animal models of obesity. The over consumption of fructose-sweetened beverages is particularly relevant to young individuals. Experimental short-term fructose consumption in young rodents results in increased levels of inflammatory and oxidative damage markers in the hippocampus. These studies reinforce the idea that oxidative stress and inflammation play a central role in fructose-induced damage to the brain even in offspring. In turn, studies showing increases in cerebral protein nitration followed by cytochrome c oxidase and Citrate synthase activity in the hippocampus from adult, but not young, suggest that aging might exacerbate the oxidative condition induced by this diet and this is particularly relevant since protein nitration plays a role in the progression of neurological disease. Chronic fructose consumption disrupts various cellular processes such as inflammation and oxidative metabolism which reduces the threshold for a range of neurological and psychiatric disorders. For example, visceral fat and serum triglycerides induced by high fructose consumption have been associated with anxiety and depression-like behaviors. Furthermore, it is known that fructose modulates the serotonergic system, which has important actions on the regulation of emotions and cognition.

Dietary sulfite primarily originates from preservatives in processed and dried food as well as beverages

Polyphenols present in a wide range of plant-based foods have received great interest owing to their antioxidant capacity and potential protective effect in reducing cardiovascular disease risk through improvement in vascular function and modulation of inflammation.The interpretation of the influence of polyphenols on cardiovascular health in dietary intervention studies can be complicated due to dynamic bio-availability during the processes of absorption, metabolism, distribution, and excretion. Generally, the absorption of dietary polyphenols is widely dependent on the type and structure of the compound and is often slow and largely incomplete in the small intestine. Therefore, significant quantities of polyphenols are retained in the colon. In addition, the non-absorbed polyphenols are subjected to bio-transformation via the activity of enzymes from various microbial groups . Consequently, the micro-biota-derived metabolites of polyphenols are better absorbed in the gut,which then become an important factor in the health effect of polyphenol-containing foods. Important plant polyphenols and their microbial derivatives are listed in ref . Many of the studies that assess bio-availability and effects of polyphenols have evaluated the balance between the enterohepatic circulating levels, residence time in plasma, and urine excretion rate of the parent phenolic compounds and their microbial-derived metabolites using metabolomic techniques. Importantly, although endogenous enzyme and transporter activities in the small intestine as well as transformation of polyphenols are subject to a wide inter individual variability,nft channel the functional capability of the gut micro-biota is important to partially explain the variation of bio-availability among the population.

Assessing the properties of a single dietary constituent from the polyphenol family alone without dietary fiber is difficult due to the complex dietary food matrix present in a flavonoid-rich diet. For example, regular consumption of apples increased the numbers of fecal bifidobacteria and decreased the C. perf ringens count.Similarly, the concomitant dietary presence of apple polyphenols and FOS increased SCFA production.In contrast, compared to consumption of an inulin-containing diet alone, including a grapefruit flavonoidrich extract decreased both production of SCFAs and the bifidobacteria population.Furthermore, a randomized crossover intervention study in which subjects consumed high levels of cruciferous vegetables for 14 days revealed an alteration of the fecal microbial community profile compared with a low phytochemical, low-fiber diet, including a higher abundance of Eubacterium hallii, Phascolarctobacterium faecium, Burkholderiales spp., Alistipes putredinis and Eggerthella spp.The observed changes could also be explained by the increase in dietary fiber that is enriched in cruciferous vegetables.200 Overall, the direct effects of fiber blur the ability to judge the specific effects of individual dietary ingredients on gut micro-biota. These dietary ingredients may act in an additive or a synergistic manner, exerting their effects on gut micro-biota. The prebiotic-like flavonol-rich foods have been demonstrated to modify the composition of gut micro-biota. Six week consumption of a wild blueberry drink that was high in polyphenols was shown to increase the proportion of Bifidobacterium spp. compared to the placebo group; however, a high inter individual variability in response to the dietary treatment was also observed.Similarly, the daily consumption of a high-cocoa flavonol drink for 4 weeks significantly enhanced the growth of fecal bifidobacterial and lactobacilli populations, but decreased the Clostridia histolyticum counts relative to those consuming a low-cocoa flavonol drink .

Furthermore, unabsorbed dietary phenolics and their metabolites selectively inhibit pathogen growth and stimulate the growth of commensal bacteria. For example, grape pomace phenolic extract increases Lactobacillus acidophilus CECT 903 growth in liquid culture media.In addition, upon bacterial incubation, tea phenolics were shown to suppress the growth of potential pathogens such as Clostridium spp. and Gram-negative Bacteroides spp., whereas commensal anaerobes such as Bifidobacterium spp. and Lactobacillus spp. were less affected.Similarly, the flavanol monomer -catechin significantly increases the growth of the Clostridium coccoides−Eubacterium rectale group, Bifidobacterium spp., and E. coli and significantly inhibits the growth of C. histolyticum group in vitro.To date, there is a wide range of phenolic compounds that have been demonstrated to have antimicrobial properties, and many have been previously reviewed.Although many of the studies highlighting the beneficial role of plant polyphenols through regulation by gut micro-biota appear promising, there are limitations in the results that can be drawn regarding the ability of flavonoids to influence the growth of selected intestinal bacterial groups using a batch-culture model. More comprehensive human intervention studies will be essential in the future to provide insight into the potential influence of dietary polyphenols and their aromatic bacterial metabolites on intestinal microbial communities and their activities.Probiotics are defined as viable microorganisms that, when consumed in sufficient amounts, confer a health benefit on the host.To date, most of the commonly used probiotics are limited to strains of certain Lactobacillus and Bifidobacterium species .

Survival during passage through the GI tract is generally considered as the essential feature for probiotics to preserve their active functions in the colon. Indeed, the probiotic strains must overcome biological barriers, including resisting gastric and bile acid secretion and tolerating intestinal lysozyme and toxic metabolites produced during digestion . Various studies found that at least a fraction of probiotic bacteria can be detected in stool for between 1 and 3 weeks after consumption . Probiotic Lactobacillus strains were also found to adapt for survival in the gut and possess gut-inducible genes that are responsive at different sites in the intestine.Interestingly, provision of the probiotic Lactobacillus plantarum to mice fed a Westernstyle diet and to humans resulted in similar gene expression profiles of this strain.As probiotics are delivered via various food vehicles, the complex food matrix should also be viewed as an important factor that may alter the probiotic activity in the gut. To date, only a few animal and clinical studies have addressed the functional roles of food on probiotic-conferred health benefits.The mechanisms of probiotic effects on health are only partially understood but likely function either directly through interactions with host intestinal epithelial and immune cells or indirectly by modulating the indigenous intestinal micro-biota. In regard to the latter, several studies have concluded that probiotic consumption does not result in global modifications of the intestinal micro-biota in healthy individuals.However, probiotics might confer modest but significant changes to the functional activities of local intestinal bacterial populations. When examined at the meta-transcriptional level, intake of a probiotic fermented milk was associated with the upregulation of microbial genes corresponding to plant polysaccharide metabolism.Similarly, administration of probiotics was shown to induce crosstalk between the probiotics from the diet and the individual bacterial species in the gut and might induce competition for limited substrates that results in fluctuations tof the metabolic profile of the host.The gut micro-biome of healthy adults is highly resilient , where the stable native micro-biota prohibits the succession of microbes from the diet.In addition, the effect of probiotics on the gut micro-biome appears to differ depending on host phenotypes such as age, health status, and chronic conditions. For example, the infant gut micro-biome is highly diverse and dynamically changes during development and therefore may be easily influenced by the consumption of probiotics . In individuals with irritable bowel syndrome , probiotic consumption resulted in an increase in the numbers of Bacteroidetes in the intestine.Moreover,hydroponic nft intake of two Lactobacillus strains by diet-induced obese mice altered microbial composition and decreased expression of inflammatory genes in the adipose tissue while increasing levels of fatty acid oxidation in the liver.Further studies are needed to investigate the effects of assorted probiotic supplements on the gut micro-biome with respect to various host life stages and phenotypes.

The premise behind substituting sugar with artificial sweeteners is to maintain the palatability of food at the same time as lowering energy intake. However, a sufficiently high ingestion of non/low-digestible sugar substitutes stimulates the growth of gut micro-biota and can induce transitory diarrhea in humans.In particular, the great proportion of non/lowdigestible sugar substitutes that reach the distal intestine are subject to fermentation by the colonic micro-biota, offering approximately 2 kcal/g of energy.Although discovering and characterizing these compounds within foods is relatively new, it is of interest to note that many of these food ingredients are common in our daily diet. For example, the disaccharide alcohol maltitol is considered a common replacement for sucrose. Urinary and fecal excretions of sorbitol and maltitol after 24 h in conventional rats were shown to be minimal compared with germ-free rats.Likewise, maltitol consumption significantly increased production of SCFAs in addition to nine tested fecal microbes after a 6 week trial, including bifidobacteria, Bacteroides, Clostridium, lactobacilli, eubacteria, Atopobium, Fusobacterium prausnizii, Ruminococcus flavefaciens, and R. bromii. A 12 week administration of Splenda, composed of 1.1% of the artificial sweetener sucralose, increased fecal pH and reduced the amount of fecal bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria in a rat, whereas isomalt, a widely used low-energy sweetener, was considered to be bifidogenic in a human study.Overall, artificial sweetener fermentation by gut micro-biota remains either unexplored or poorly documented, some of which are highlighted in a review by Payne et al..Azo compounds are widely used as coloring agents in foods, beverages, and food packaging.In addition, azo polymer coatings have been specifically designed for colon-selective drug delivery due to the presence of pH-sensitive monomers and azo cross-linking agents in the hydrogel structure.Indeed, azo dyes can be metabolized under anaerobic conditions by intestinal microbial processes and, as a result, produce the reductive cleavage products aromatic amines . The majority of the toxic effects of azo dyes are exerted through aromatic amines produced by their colonic degradation.Raffi et al. reported that isolated intestinal bacteria in an anaerobic culture system were able to decolorize the dyes in the supernatant, suggesting that some of the azoreductase activities are extracellularly released.Xu et al. demonstrated a variable degree of efficiency in the reduction of Sudan azo dyes and Para Red by 35 prevalent human intestinal microbes in vitro.In contrast, Sudan azo dyes and their metabolites selectively inhibit the growth of some human intestinal microorganisms,which may suggest a potential impact on gut micro-biome after long-term exposure. In summary, although there are tantalizing glimpses into the effect of azo dyes on microbes in vitro, more data from animal and human studies are keenly awaited.In the colon, sulfur is present in either inorganic form or organic form .The human GI tract poorly absorbs sulfate, and there is little sulfatase activity in the mucosa of the GI tract; therefore, free sulfate in the colon is likely to be of dietary origin.Dietary sulfate drives the activity of sulfate-reducing bacteria that couple oxidative phosphorylation with reduction of sulfate to produce sulfide.The total inorganic sulfur intake is much higher in the Western diet in comparison to a typical African rural diet. Highly processed foods that are high in sulfate include bread, soy flour, dried fruits, and brassicas, as well as sausage, beers, ciders, and wines.Sulfur-containing amino acids such as cysteine can be found in dietary protein and are a source of sulfur for colonic sulfate-reducing bacteria Desulfovibrio desulfuricans.Native Americans who consume a diet high in resistant starch and low in animal products harbor significantly distinct sulfate-reducing bacterial populations and more diverse and different methanogenic archaea than Americans consuming a typical Western diet.Substrate competition for hydrogen among methanogenic archaea, sulfate-reducing bacteria, acetogenic bacteria, and otherspecies likely occurs in the colon.Because hydrogen is an essential component for the survival of colonic methanogens, removal of the substrate terminates methanogenesis. Given an adequate supply of sulfate, sulfate-reducing bacteria that are more abundant in the right colon outcompete methanogenic archaea for H2 due to their higher substrate affinity to produce hydrogen sulfide , an end-product of dissimilatory sulfate reduction.As a result, the mucosal micro-biome may be shaped in part through the availability of toxic sulfide compounds and the differential susceptibility of mucosalistic microbes to the toxins.Furthermore, the activity of methanogenic bacteria can also be disrupted by bile acids. In brief, methane production was thought to occur only when sulfate-reducing bacteria were not active.If sulfate is limited and hydrogen is in relative excess, methanogenic bacteria or perhaps acetogenic bacteria will become essential.Therefore, the levels of sulfate present in the colon are critical for determining which bacterial group gains a better survival advantage.Alcohol. Many people consume alcoholic beverages; however, few studies exist on the effect of alcohol consumption on the gut micro-biome of healthy individuals. For individuals who consume alcohol to excess, abnormal gut micro-biota and bacterial overgrowth can potentially initiate or worsen alcohol induced impaired gut barrier function and contribute to endotoxemia in patients with alcoholic fatty liver disease.

The role of date polyphenols has been explored on a number of cardiovascular parameters

An in vitro study, using a colorimetric assay, demonstrated a Brazilian date fruit could inhibit angiotensin-converting enzyme activity, a potentially important target mediating blood pressure both in the pulmonary circulation and endothelial cells. Results from in vitro oxidant defense assays have been further supported by ex vivo and in vivo animal studies. These studies demonstrated positive effects of different date cultivars against a variety of toxicants that produce free radicals, including carbon tetrachloride, isoproterenol , cadmium, and from the oxidant-generating streptozotocin-induced diabetic rat model. The protective effects of dates against oxidative stress were attributed to improved activities of oxidant defense enzymes such as catalase , superoxide dismutase , glutathione peroxidase, glutathione reductase, and glutathione S-transferase, along with a significant reduction in malondialdehyde. Moreover, dates were demonstrated to diminish oxidative damage, inflammation and apoptosis in cardiac tissue of ISO-treated rats. Oral administration of lyophilized Ajwa date extract down regulated the expression of pro-inflammatory cytokines and apoptotic markers in injured Wistar rat heart tissue, further supporting the anti-inflammatory and anti-apoptotic potential of dates against ISO-induced myocardial damage. A more recent study investigated the possible cardioprotective effects of a nanopreparation mix of Ajwa date fruits and seeds on doxorubicin -associated cardiotoxicity in Wistar rats by studying hemodynamic, electrocardiological, and biochemical change. The results obtained suggest that rats pre-fed 1.4 g/kg of the preparation one hour before DOX infusion were protected from a significant elevation in left ventricular pressure observed in the control group.

In addition, pretreatment with the preparation prevented DOX-associated ischemia and increased the antioxidant capacity of reduced glutathione in cardiac tissue,blueberry package compared with the untreated group. Quantification of Ajwa pits and a mixture of Ajwa fruit/pits reported that the pits contained 47.4 g/kg of total flavonoids, while the mix of pits with fruits contained 23.8 g/kg of total flavonoids, including epicatechin-phloroglucinol and epicatechin.Extracts of high concentrations of phenolic and flavonoid compounds in four different varieties of dates exerted favorable effects in protecting and repairing tissue injury following myocardial infarction induced either by ISO or temporary ligation of the left anterior descending coronary artery in a rodent model via oxidant defense activities and mobilization of circulating progenitor cells from bone marrow and peripheral circulation. In this regard, oral pretreatment with date extracts for a period of 28 days prior to ISO injection significantly improved the state of MI compared to the control group. Elevated levels of glutathione, SOD, and CAT, and reduced levels of thiobarbituric acid reactive substances in heart tissue of rats were noted. A dose-dependent effect was evident in which 400 mg/kg had significantly greater effects compared to 200 mg/kg in most cases. Interestingly, following MI induction, compared to controls, date extracts significantly increased circulating levels of CD34 and CD133 positive progenitor cells that are involved in tissue repair. The quantity of total phenolics in the dry plant material varied from 21.53 ± 0.90 to 26.82 ± 0.92 mg GAEs/g and from 2.90 ± 0.13 to 4.92 ± 0.21 mg quercetin/g.A limited number of studies in animals has suggested beneficial effects of dates on plasma lipids. Golden Syrian hamsters fed a high cholesterol diet supplemented with 50% Khalas date pulp for 13 weeks showed significant decreases in plasma cholesterol, triglycerides and LDL-C compared to those consuming the high cholesterol diet alone.

Interestingly, the addition of dates to the high cholesterol diet significantly increased liver triglyceride levels compared to the high cholesterol diet alone. Although the mechanisms underlying this liver lipid-loading effect are not clear, fructose, which is present in dates, has been shown to stimulate hepatic triglyceride synthesis when consumed with a hypercaloric diet. Unfortunately, insufficient information was provided regarding the composition of the chow and high cholesterol diets , or how liver cholesterol and triglyceride concentrations were measured, limiting the interpretation of the reported effects. In another study, hyperlipidemia-induced albino male rats fed either 300 or 600 mg/kg body weight of Aseel date fruit suspension for eight weeks showed significant reductions in triglycerides and very low-density lipoprotein compared to the control group. Curiously, serum levels of cholesterol, LDL-C, HDL- cholesterol and the LDL-HDL ratio were also significantly decreased at the intake of 300 mg/kg but not at 600 mg/kg. Results from the animals receiving date intake at 300 mg/kg approached the same response as the positive control group receiving atorvastatin . While intriguing, these data must be interpreted with caution, since rodents have a different absorption, distribution, metabolism and excretion profile for lipids compared to humans. A search of English- and Arabic-language databases revealed two human studies on date intake. One is a pilot trial with ten healthy non-smokers consuming 100 g/day of either Medjool or Hallawi dates for four weeks in a crossover design with a four-week washout between groups. A significant 15% reduction in serum triglycerides with Hallawi dates was noted compared to baseline values. However, the baseline triglyceride levels for those who consumed Hallawi dates were considerably higher than that of the Medjool group, although the actual values are difficult to assess since they are only presented by a bar graph.

The study also noted that the intake of Hallawi, but not Medjool dates, significantly reduced markers of oxidative stress, as measured by the TBARS assay, the 2,20 -Azobis hydrochloride-induced serum lipid peroxidation method, and increased serum paraoxonase 1 aryl esterase activity, an enzyme necessary to protect serum lipoproteins from oxidation. The beneficial reductions in oxidative stress after consuming Hallawi, but not Medjool dates, could be related to the total phenolic concentration, which was significantly greater in the Hallawi dates by 20% to 31%. Although the major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, only Hallawi dates contained a significant portion of catechins, which have been reported to exert potent oxidant defense actions. Differences in absorption, metabolism, and bio-activity of the different phenolic compounds in the two date varieties may also help explain the disparate outcomes. Unfortunately, the inclusion and exclusion criteria for participants was poorly defined, and no data were provided regarding whether a return to original baseline values were noted after the washout and crossover period. Due to the high fiber content of dates, which can alter gut micro-biome profiles, the influence of a carry-over effect from the intake of one date variety to the next must be considered. Future study designs would ideally include a separate, no-intervention control group as well as a parallel arm design, or ensure that the primary lipid outcome measures along with the gut micro-biome milieu at the start of the second intervention period returned to original baseline values. A second human study assessed the effects of the daily intake of three Khudary dates for 16 weeks among 100 Bahraini adults with diabetes and control group consuming no dates [n = 50]. This randomized, controlled, parallel-arm study trial reported a significant improvement in the date group in plasma cholesterol levels of approximately five percent from baseline, along with a trend for reduced LDL-C. However, the results did not reach statistical significance when thetreatment group was compared to the control group, suggesting that some of the reduction in cholesterol may have been due simply to participation in the project, independent of date intake. Other limitations include lack of details regarding the actual weight of dates provided,blueberry packaging and the overall macronutrient distribution and quantity of the diets. Taken together, the reports above suggest that dates can improve markers of cardiovascular health, particularly plasma lipid levels, indices of oxidative stress and inflammation, and circulating progenitor cells. These results are primarily from in vitro and animal models, which may be useful as pre-clinical models. Unfortunately, differences in study design, the amount and composition of dates or extracts tested, and lack of details about the control groups fail to provide specificity and limit the ability to draw conclusions about mechanisms and applications to humans. The selection of a control item is important when investigating cardiovascular effects of date products or extracts, because controls can have significant amounts of bio-active compounds that can potentially affect cardiovascular function. Polyphenols are among the most studied categories of dietary phytochemicals in relation to vascular health, and the subgroups of flavanols, anthocyanins and proanthocyanins have been of particular interest. Intake of flavanol- and PAC-rich foods and food extracts from strawberries, blueberries, and cocoa have demonstrated improvements in vascular markers that are associated with markers indicative of improved cardiovascular health. Several molecular mechanisms contribute to the physiological effects of flavanols, including enhancement of vasodilation through the induction of NO , free radical quenching , inhibitory effects on select prooxidants , and reduction in ET-1 activity.

Effects of dietary flavanols on markers of cardiovascular health have been discussed in detail elsewhere. Date cultivar and degree of ripeness are major determinants regarding their polyphenolic composition, as discussed above. Phenolic-acid and flavonol fractions isolated from Amari and Hallawi dates at the tamer stage were examined in vitro for antioxidant and antiatherogenic properties. The two fractions exhibited variable capacities to reduce ferric ions , scavenge radicals and inhibit LDL-C oxidation via TBARS and lipid peroxide assays, with the flavonol fractions showing the strongest effects. Only the flavonol fractions stimulated cholesterol removal from macrophages. The yields of isolated fractions in terms of µmol GAE per g fruit were considerably larger for Amari dates by approximately 10- and 3.5-fold for phenolic acids and flavonols , respectively. The two isolated fractions contained ferulic acid as a major component and comparably small amounts of coumaric acid, but differed considerably in the composition of their complementary set of phenolic acids. Amari dates contained primarily caffeic acid derivatives, whereas the Hallawi variety contained mostly a salicylic acid derivative. Seven prominent peaks of flavonols were evident. Based on an authentic standard library, all seven flavonols were tentatively classified as kaempferol derivatives. The two isolated fractions of date flavonols differed considerably in composition. In addition to one prominent flavonol peak shared by the two fractions, Amari consisted of significant amounts of five other flavonols, whereas Hallawi contained a single unique flavonol as the major component. The results demonstrated strong structure-activity relationships for date polyphenols and identified date flavonols as potential antiatherogenic bio-actives. Polyphenols derived from date syrup at concentrations of 60 and 600 µg/mL, predominantly from cinnamic acid and catechin derivatives, were found to significantly attenuate IL-6, IL-8 and vascular endothelial growth factor in human vascular endothelial cells. These observations corresponded to asignificant reduction of both cyclooxygenase-2 and VEGF induced by TNF-α at both the protein and gene expression levels in the assessment of inflammatory-associated angiogenesis in HECVs. Many polyphenols found in dates have been studied as isolated compounds in in vitro and ex vivo systems with respect to their effects on markers of vascular function. Protocatechuic acid, a metabolite of the anthocyanin cyanidin-3-glucoside , and its phase II metabolites were effective in modulating the production of the key inflammatory mediators IL-6 and vascular cell adhesion molecule-1 at dietary-relevant concentrations as low as 100 nmol L1 , with maximum reduction observed for the sulfate conjugates in human umbilical vein endothelial cells stimulated with either oxidized LDL or a cluster of differentiation CD40L . In the same study, C3G and its metabolites reduced IL-6 production in CD40L-stimulated cells, whereas both C3G and its metabolite, ferulic acid, reduced VCAM-1 production. Anthocyanins and ferulic acid have also been found to significantly reduce monocyte adhesion to HUVECs under physiologically relevant conditions, an important step in reducing atherosclerosis development. In human intestinal cells in vitro, the addition of a freeze-dried date extract from California-grown dates with a total proanthocyanidin content of 13% was demonstrated to act as a potent co-agonist ligand for the farnesoid x receptor , a nuclear structure important for maintaining triglyceride and cholesterol homeostasis. This study provides a potential mechanism by which dates may exert a hypotriglyceridemic effect, as observed in the human study noted above. The tea catechin, epigallocatechin- 3-gallate , has also been shown to modulate FXR in a tissue- and gene-specific manner. Further studies are warranted with dates and their extracts using both wild-type and FXR knockout mouse models. While the above in vitro work is promising, data from dietary interventions that specifically examine the association between circulating date polyphenols or phenolic metabolites with physiological effects have yet to be reported.

Starch accumulates linearly across the daytime at an almost constant rate

Starch, or the proportion of the amylose fraction of starch, is used as a common ripening biomarker for apple, banana, and pear. This marker relies on the ability of amylose to physically interact with iodide to form a triiodide blue-black complex. Starch can also influence the quality of fruit juice. Although starch is degraded to sugars when fruit ripens, this conversion is not complete. Ripe fruit processed for juice therefore contains starch, which is treated with amylases for clarifcation. Further, the amylose content of the remanant starch in some fruit processed for juice, may alter juice viscosity.Prepackaged leafy greens are convenient and healthy, and are popular options for salads in western countries. Metabolism in this horticultural product can be considered over distinct phases in its lifecycle: pre- and post harvest. In developing spinach, the photosynthetic organ, i.e., the leaf, fixes carbon, and partitions a large portion ~20% to starch biosynthesis during the light period under lab conditions . During the night, the leaf starch is degraded into sugar, to maintain plant metabolism, resulting in an empty polysaccharide reserve before the next light period. In Arabidopsis, the expression of SBEs and the changes of amylopectin and amylose show a similar trend, but there is variation in when SBE transcripts peak. Although there is no information on SBE transcriptional levels in spinach during the diel,nursery grow bag there may be some similarities with Arabidopsis because the pattern of leaf starch accumulation is comparable in spinach and Arabidopsis. The preharvest starch reserve may alter the postharvest quality of leafy greens.

Harvested green produce are stored in optimized packaging under limited light exposure conditions which restricts new energy and carbon input from photosynthesis. However, respiratory activity, which is the carbon skeleton generation process for cellular metabolites, although reduced, does not stop. In detached leaves, the starch can be broken down to glucose, and sugars become the main source of fuel for cellular metabolism and ATP generation in the early stage of respiration . In the late stage of the respiratory process, the depleted sugars will be replaced by proteins, lipids, and membranes, triggering leaf senescence and cell death. Tis results in undesirable produce quality and ultimately, in produce loss. Preharvest and post harvest starch content may determine post harvest energy reserves and influence the time span that buffers the onset of senescence, thus influencing shelf-life of harvested green leaves. Correlations between leaf starch content and post harvest longevity have been found. For example, lettuce and red chard harvested at the end of the day, when leaf starch content was highest, had a longer extended shelf-life than organs harvested at other times of day. This may not be true of all varieties e.g., salad roquette. Starch also correlated with improved shelf-life quality after light exposure to detached leaves in vegetables such as Chinese kale and lettuce. The accessibility of sugars from the degraded starch may relate to leafy-green quality, and the upregulation of SBEs would convert amylose to the more catabolically available amylopectin, providing a more readily available source of sugar.The amylose-to-amylopectin ratio in Arabidopsis influences flowering time and reproductive growth, key markers of development, and fitness. Whether starch molecular structure and composition influences the preharvest growth of leafy greens in a similar way, remains unknown, but it seems likely.

Potato, sweet potato, and cassava are generally considered as high glycemic index foods because the starch in their storage organs is easily digested to sugars when consumed, leading to a rapid increase in blood sugar level. It is established that high GI food exacerbate metabolic disorders such as diabetes and obesity. In contrast, multidisciplinary experimental research shows that digestion-resistant starch could increase the healthful microbial communities of the gastrointestinal tract, reducing the occurrence of constipation, and lowering the risk of colon cancer. Altering potato starch composition is a viable way to increase ‘dietary fiber’ content and to enhance colonic health. This can be achieved by either physical, chemical, or enzymatic modifications of purified starch, e.g., etherification, esterification, or by fine-tuning the activity of starch biosynthetic enzymes. Reduction or knockout of SBEs in a range of species have reliably led to an increase in the resistant starch content in various species including horticultural crops e.g., potato, sweet potato, and cassava. Interestingly, SBE2 is not the dominant isoform expressed in storage tubers and roots, but it exerts a major function in amylopectin synthesis. Very high levels of RS can be achieved by the combined suppression of SBE1 and SBE2, but with a yield penalty. The transcriptional profiles and functions of SBE3 are unclear in the developing tubers . In addition, potato tubers suffer from a post harvest disorder: cold-induced sweetening . Potato tubers are stored at low temperatures to extend shelf life and to meet year-round demand. However, sugars accumulate from starch breakdown, a process referred to as CIS. Although a problem for the potato industry, CIS could be a mechanism to allow tubers to cope with chilling stress. CIS negatively affects the quality of fried or baked potato products: reducing sugars react with free amino acids at high temperature cooking through the Maillard reaction, to form carcinogenic acrylamide.

Changes in the enzymes involved in starch biosynthesis and degradation are involved in CIS. SBEs are actively expressed in CIS susceptible tubers, and in StVInvsilenced, CIS-resistant tubers, SBEs transcriptional level were suppressed. Naturally occurring high RS potato varieties, also, have less susceptibility to CIS. Therefore, evidence points to a positive association of SBE activity with CIS severity in some potato genotypes.Starch is a major component of the dry mass of fruits at commercial harvesting time. Starch is transiently synthesized and stored in unripe fruits with a peak just before ripening. Starch appears to be a critical feature of climacteric fruit metabolism, known for their bursts of respiratory activity and ethylene production upon ripening. Climacteric fruits contain more starch, and, more active starch biosynthesis than non-climacteric fruit after anthesis. In tomato, the functional genomics model for freshy climacteric fruit, starch fulfilled 40% of the carbon needed for respiratory processes based on a constraint-based flux model. Experimental evidence from post harvest metabolism also supports the model: tomato fruits stored post harvest under low or chilling temperatures undergo bursts of stress-related carbon dioxide and ethylene production when allowed to recover at room temperature, with an accompanying and corresponding decrease in starch reserves. A similar inverse relationship between starch content and respiratory activity was observed in ripening banana, ginger rhizomes sunberry, apple and durian. Te relationship between tissue starch content and respiration may not be perfectly linear in all species, e.g., in stored ginger, starch showed a biphasic accumulation pattern as respiration progressed, a trend not seen in other tissues examined . Furthermore, the relationship between these variables may also differ among genotypes within a species. Apart from climacteric characteristics, after the onset of ripening, starch content plummets sharply accompanied by starch decomposition into soluble sugars, and the total soluble sugar content continues to rise proportionally . This dynamic metabolic process had been reported for both climacteric and non-climacteric species including tomato, apple, banana, plantain, mango, kiwifruit, pear, and strawberry. Adequate storage of the starch-derived soluble sugars, is essential to produce an acceptably favored horticultural produce of appropriate sweetness. Accompanying the starch-sugar dynamics,plastic growing bag amylopectin-to-amylose ratio , also changes interactively . The difference in the AP/AM ratio in fruit development is expected to influence the structure of starch and its degradability. In the ripening tomato, the rate of decrease of amylose was greater than that for amylopectin . Thus, the AP/AM ratio increased dramatically during ripening, in concert with the increase in soluble sugar content and fruit color change from green to red. This phenomenon where the proportion of amylopectin increases relative to amylose, was also evident in ripening apple and banana. It is possible to speculate that of the available starch left during fruit ripening, the amylose, or long chained amylopectin was converted into amylopectin whose branch-like structure has a much higher susceptibility to enzyme attack, allowing the rapid process of starch degradation into soluble sugars and supply for respiration. However, this mechanism may not be universal for all fruit. For example, the changes in AP/ AM ratio in kiwifruit are similar to those in developing potato tubers, where the ratio of AP/AM almost remains constant during tuber development. In ripening tomato fruit with sharp increases in AP/AM, up-regulation of SBEs transcriptional expression is expected. Among SBEs, the class 2 SBE has the major effect on altering starch compositions .

Elevated expression of SBE2 transcripts does parallel the changes in the AP/AM in ripening tomato, apples, and banana. We propose that ultimately, this change in glucan structure indirectly contributes to favor, quality, and commodity value.Starch, in general, plays an essential role in balancing the plant’s carbon budget as a reserve of glucose that is tightly related to sucrose metabolism and sugar signaling pathways. Starch is considered as an integrative mediator throughout the plant life cycle, regulating plant vegetative growth, reproductive growth, maturation and senescence, and response to abiotic stresses. This comprehensive regulation is achieved by changes in the synthesis and degradation of starch to balance glucose levels, after developmental and environmental triggers in different organs. Transitory starch and its biosynthesis have been well studied in the model plant Arabidopsis, but little research has been conducted on post harvest leafy greens. Quality metrics such as shelf-life, favor, color, firmness, and texture are of consumers’ choice, and they are related to the limited pools of storage compounds in detached leaves, which cells rely on to maintain basic cellular activities. A hypothesized function for the starch in packaged leaves could be presented as such: starch may act as a bufer against sugar starvation, and protect against cellular autophagy, by serving as an alternative energy source. If the biosynthesis and degradation of starch could be adjusted in a controlled way, then the modulated release of sugars may influence the post harvest shelf-life in detached leafy greens . A continuous, paced supply of sugars may preserve vacuolar nutrients and water content, leaf cellular structure and integrity, and, thus extend the ‘best by’ post harvest date of the produce. Although the eco-physiological role of amylose is poorly understood in Arabidopsis, the AP/AM ratio may set a threshold for the optimum usage of starch. SBE action in leafy crops may differ from those in Arabidopsis given the dissimilar numbers of their isoforms and domain features . Modifying the quantity and quality of the starch in leafy greens such as spinach, lettuce, and watercress, by targeting starch bio-synthetic enzymes, may provide evidence to its post harvest function in terms of produce longevity. Resistant starch is a popular nutritional additive to produce food with enhanced quality attributes, i.e., higher fiber content, and starchy horticultural commodities are similarly attractive. Te yield penalty of high amylose crops may be alleviated by picking an ideal AP/AM ratio through a coordinate change in the relative balance of starch bio-synthetic enzymes. In the case of potato, it is plausible that down regulation of SBEs not only produces healthy fiber-starch, but also lessens the CIS severity and acrylamide problem . However, the sugars derived from starch during CIS may be an adaptive mechanism to enhance plant chilling tolerance. Rapid sugar accumulation upon cold stress have been reported in fruit . The sugars freed from starch may promote metabolic activity and serve as an osmoprotectant, thus alleviating chilling injury. Te major functional SBEs were found to be upregulated in cold-stressed banana fruit, potato tuber, and Arabidopsis leaf, which may facilitate the ‘sugaring’ process. Modulating SBE activities may alter the rate of sugar released from the highly digestible starch polymers, thus changing the fruit/tuber cold responses. In fruiting species, the importance of ‘transitory-storage starch’ may be underestimated due to the lack of enough direct knowledge of its function, gained from experimental data. Tomato serves as a functional genomics model for feshy fruit, as it is easily transformed and genetically manipulated. The putative function of ‘transitory-storage starch’ in fruit ripening, respiration, and sweetness enhancement may be revealed by engineering AP/AM ratio through over expression or suppression of SBEs. We hypothesize that high amylose, resistant starch tomato fruit may have reduced available starch, sugars, and changes in fruit ripening and other processes that are dependent on starch as a carbon supply and source of energy post harvest. Tomato SBEs may not reffect the functionality of all fruit SBEs, but it would produce fundamental knowledge and expand our understanding of species-, organ- and developmental-specifc regulations of the core starch bio*synthetic enzymes.

Diapause is an understudied phase of the life cycle for bumblebees and many other groups of insects

Our study showcases the value of field-based research in understanding diapause as a potentially vulnerable or robust stage in an insect’s life history.Lab-based studies that monitor bumblebee vital rates under controlled conditions will remain foundational in the effort to identify the environmental factors which impact diapause survival. However, lab-based studies cannot capture the real-world environmental pressures faced by diapausing insects, and lab-reared colonies cannot replicate the adaptive capacity of wild colonies to cope with these pressures. In demonstrating the utility of B. impatiens as a model system for exploring insect overwintering ecology, we are hopeful that our research will pave the way for future field-based studies targeting this life cycle stage.Our cultural context shapes our interactions with the world and dictates the way we visualize, process, and utilize information. For example, holistic and analytic modes of thought differs across cultures , with people from East Asian, collectivistic cultures typically exhibiting holistic thought and people from Western, individualistic cultures exhibiting analytic thought . Holistic thought associated with an East Asian perspective is primarily dictated by context and relational cues. In this style of thinking, people are more likely to attend to background information and relationships, viewing the system as a whole rather than a sum of its parts . For example, in the classic narrative task, participants view an image of a fish bowl and describe what they see in as much detail as possible for one minute . Holistic thinkers, in this task, are more likely to name background or environmental objects like “under the water.” Analytic thought, in comparison,black flower bucket is characterized by attention to foreground information and discriminating/categorical qualities .

In the narrative task, analytic thinkers are therefore more likely to name foreground objects like “fish” and describe their properties and movements. Previous research has predominantly focused on collectivist and individualist cultural differences in different thinking styles, and factors that could explain the culturally bounded phenomenon . For instance, researchers have examined the role that environment plays in perception, exposing participants to images of cityscapes . These researchers found that images of Japanese cities were more ambiguous and contained more elements than images in American scenes, presumably priming participants to attend more carefully to context. Indeed, when primed with images of a Japanese city, both American and Japanese participants were more likely to think holistically. In addition to environmental differences, language might also play a role. For instance, in one study, researchers examined whether thinking styles influence attention and awareness. To test this, participants were shown the classic fish bowl vignette, and researchers used an eye-tracking device to measure eye fixation patterns. East Asian and Western participants showed non-significant differences in looking patterns . However, the emergence of holistic and analytic thoughts occurred when participants were asked to describe the scene, where East Asian participants were more likely to name background and environmental information than Westerners did. Since differences were only observed when participants were asked to describe the image, researchers suggested language as a mechanism for divergent thinking styles. Language differences could explain sub-cultural differences as well. Two studies found differences even between two collectivist cultures. Korean participants thought more holistically than Chinese participants did when presented with the narrative task. Researchers proposed that these varying degrees of holistic thinking might be related to the syntactic differences in the participants’ native languages, noting that English sentences were mostly head-initial and Korean were mostly head-final.

This “head-initial/head final” judgment refers to verb/noun positioning, with head initial language leading with the noun followed by the verb, and head-final language leading with the verb followed by the noun. This hypothesis suggests a primacy effect, with speakers being drawn to whatever aspect of the sentence is placed first. English, therefore, as a head-initial language, would mention the subject first in a sentence, priming its speakers to attend to focal objects, whereas Korean, as a head-final language, would mention the subject last in a sentence, priming its speakers to attend to context and the relationship between objects. Since Chinese alternates between head-initial and head-final languages, Chinese speakers showed a lesser degree of holistic thinking than Korean speakers. Results from other studies support the idea that language properties could associate with the measured thinking styles across individuals, situations, cultures, and even subgroups within the same culture . So far, the literature has suggested thinking styles as a static characteristic of members of a culture, and unique features of language could foster a certain type of thinking style over a long-term exposure. Little is known how language could potentially influence thinking styles as a contextual factor from moment to moment. For example, studies have used tasks with categorical or relational associations of concepts to measure holistic and analytic thinking styles. One influential study constructed triads with both a categorical and relational choice. Participants were asked to choose the two words that were most closely related . If the participant grouped policeman and postman, this would be categorical, indicating an analytic choice, whereas policeman or postman grouped with uniform would be relational, indicating a holistic choice . However, ample studies have shown that the strength of categorical and relational associations can vary across pictorial and verbal formats . In general, pictorial stimuli yield a stronger categorical association based on semantic feature overlaps, whereas verbal stimuli yield stronger relational associations based on word associations. Consequently, the verbal triad could “benefit” relational associations more whereas the pictorial triad could “benefit” categorical associations. Therefore, it is possible that the measured thinking style could be dependent on the format of the triad task. Furthermore, categorical associations could be manifested in the verbal labels of object names. For example, some semantic categories are emphasized in their names, such as “berry ” and “nut ”.

Having these verbal labels in object names could potentially emphasize the categorical associations of concepts, influencing the thinking styles in different ways. On the one hand, since the categorical association is related to analytic thinking in the triad task, highlighting the categorical information could lead to more analytic thinking . On the other hand, highlighting the categorical information via verbal labels of object names could potentially promote a focus on similarities of objects, a feature of the holistic thinking style . Anecdotal evidence is in alignment with this argument. Specifically, this feature is extremely pervasive in some Asian languages, such as Mandarin Chinese, but not so much in Western languages such as English. Chinese names of objects commonly include the category label alongside the noun, such as the verbal label “flower ” in “rose-flower ”, “daisy-flower ”, and “peony-flower ”. Potentially, having this language feature in Mandarin Chinese promotes a focus on overall similarities of objects, fostering holistic thought in Chinese speakers. The overarching goal of this study is to examine how language might impact thinking styles, by using verbal labels to create different contexts when measuring people’s thinking styles. Study 1 sought to examine whether thinking styles measured in a classic triad task could be shifted using verbal labels instead of pictures. Given the evidence that relational associations are stronger in verbal format,square black flower bucket we anticipated that people would show more holistic thinking when tested with verbal format in comparison to pictorial format. Study 2 aimed to examine whether participants could shift their thinking styles measured by the verbal triad task, after being verbally primed to focus on categorical associations of objects. Two potential outcomes were predicted according to two competing hypotheses . If the effect of verbal labels is direct , we would expect that the categorical labels in object names would make people focus on the categorical associations of words, and choose categorical associations more . However, if the effect of verbal labels is indirect, we would anticipate that exposure to these category labels in object names could make people focus on the overall similarities of objects, and they would show a shift to holistic thinking and choose more relational associations. In addition, we explored potential gender differences in measured thinking styles since studies have shown that females and males could differ in their analytic skills and intuitive-analytic thinking .The different thinking styles, namely, analytic vs. holistic, have been long associated with Western and East Asian cultures, respectively. Our findings from two studies have provided some preliminary evidence that thinking styles of native English speakers, especially when measured by verbal formats, are highly variable across individuals and context dependent. In Study 1, we showed large individual differences in thinking styles, and when measured with a verbal format, more individuals became holistic thinkers from analytic thinkers compared to when measured with a pictorial format. In Study 2, we used an experiment to demonstrate that exposure to verbal labels highlighting the categorical associations would lead participants, especially females, to prefer categorical candidates in the verbal triad task. These findings converge on the idea that thinking styles can be variable instead of static, and language can impact thinking styles of individuals from moment to moment.Results from Study 1 and Study 2 may seemingly be contradictory since Study 1 suggested that people became more holistic thinkers with the verbal triad task whereas in Study 2, participants were shifted to analytic thinkers after being primed with verbal labels.

However, they actually converge on the observation that language could impact thinking styles, but the exact direction depends on the feature of the verbal information and the contexts. The triad tasks in Study 1 assess relative strength of categorical and relational pairs of images or words, resembling word association and semantic priming . Previous meta-reviews have pointed out that both semantic and relational associations could lead to a priming effect, but the semantic association depends on feature overlaps of objects whereas the relational association is also influenced by word association in text . In addition, a previous study has shown that the semantic priming effect is stronger in the verbal than pictorial formats . Therefore, when the triad task was implemented in a verbal format, the relational association became “boosted” so people chose the relational candidates more compared to the pictorial format. In Study 2, we primed people to focus on the categorical associations by using names that highlighted the categorical information. Specifically, the verbal labels like “berry”, “nut”, and “ball” in the prime condition made the shopping task easier to the participants if they looked for the verbal similarity. This verbal similarity would then further promote a focus on the category similarity. Consequently, participants were potentiated for the categorical association in the triad task. Thus, the influence of the verbal labels was directly “translated” into the triad task, and people tended to continue focusing on the categorical associations and chose the categorical candidates more, resulting in a shift to analytic thinking. The different results of Study 1 and Study 2 could also partially, if not all, result from the task instructions. In Study 1, we instructed participants to find candidate word/picture that goes “together” with the target word, indicating an emphasis on relationships; however, in Study 2, the shopping task required participants to “sort/separate” items, promoting some analytical processes. Nevertheless, this possibility still points to the factor that thinking styles can be viable and influenced by language. Therefore, although the influence of verbal labels shifted people’s thinking styles in the opposite directions in Studies 1 and 2, they both manifested the potential impact of language on measured thinking styles. It is worth noting that our findings mostly showed the short-term effects of language on thinking styles, since the verbal labels only created task-specific contexts when measuring thinking styles. At most, our results suggest that language could influence thinking styles and explain cultural differences in thinking styles . In particular, we want to focus on the results from Study 2. One motivation for Study 2 came from the observation that categorical associations are prevalently emphasized in Mandarin Chinese, so this feature in Mandarin Chinese could potentially cultivate a focus on the overall similarity of object categories, fostering a holistic thinking style. In contrast to this hypothesis, we did not observe that people became more holistic thinkers after being primed with categorical information. Instead, we found that categorical information made females in our sample more likely to use analytic thinking. Hence, in a Western sample, categorical information might have a direct effect, because it makes people focus on the primed category and its distinctiveness from other categories more.

The blueberry fruits were harvested throughout the ripening season in the ripe stage of berry maturity

The leaching water was collected according to the precipitation. Gas fluxes at the soil surface were sampled by the closed chamber technique, and N2O content was analyzed using a Shimadzu GC-14B. Drainage water and soil NO3 – -N concentrations were determined by the Hydrazin-reduction method . The pH of soil and drainage water was measured using 1:2.5 soil to water ratio and a Horiba D52 pH meter. The EC was measured using a 1:5 soil to water ratio with a TOA CM-14P EC meter. Leaf chlorophyll content was monitored using a SPAD meter . The NH4 + concentration of soil immediately responded to ammonium sulfate fertilization, particularly in the SC treatment. The ammonium sulfate input resulted in a higher NO3 – concentration due to nitrification. Supposedly, the SC and PM treatments had reduced nitrifier activity, thus the soil NO3 – peaks appeared one month after the SO treatment. An earlier peak of NO3 – concentration in the month of fertilization in SO indicates higher activities of nitrification compared with other treatments. The highest NO3 – concentration occurred in the PM treatment in August 2008. The pH patterns of soil strongly correlated with the amount of precipitation and fertilizer applications. The low cation content of the rainwater may enhance possibilities of leaching base cations in soil out of its profile due to their replacement. The high rainfalls in June 2008, coupled with ammonium sulfate fertilization, apparently introduced an acidifying reaction in the soil solution. The soil disturbance soon after the plantation of blueberry bushes to the containers generated a more aerobic and suitable environment for mineralization,plastic flower bucket resulting in the release of NO3 – in the early stage of the experiment.

The SC treatment originally contained high N contents derived from sewage sludge, which resulted in higher NO3 – losses in May 2008. The nitrification induced nitrate loss occurred after the first ten days of August. The SC treatment had no leaching water released from the container in the second decade of August, probably because of the dense root mat having a very active water and nutrient uptake. The other possible reason is the fast root elongation in the phenological stage around the middle of August . The total NO3 – losses of PM, SC and SO treatments were 275, 475 and 453 mg, respectively. The gradually decreasing EC patterns indicated strong leaching of base cations from the soil profile. This cation impoverishment of the media gradually became moderate in the first decade of August when the fertilizer treatment resulted in a higher cation release from the soil cation exchange sites. This fertilizer induced higher EC stabilized around the first decade of September. The plant transplantation to the containers increased the soil pore space, thus providing more aerobic conditions for microbial activity, and resulting in higher NO3 – leaching. Higher N2O emissions were detected in SC before fertilization. These may have been derived from the initially high NO3 – content in the amended material. The emission factor in SC was 0.73%. After fertilization clear fertilizer-induced N2O emissions were detected in SO and PM treatments. The emissions factors of SO and PM were 1.2 and 1.43 %, respectively. The SO represents a typical heavy textured soil widely known as having physical characteristics to emit higher N2O, compared to the light textured ones . The SO treatment was under a stronger anaerobic condition for longer periods than in the PM and SC and resulted in higher N2O emissions.

Surprisingly, the light textured PM had also high fertilizer-induced N2O flux. In general, an increase in acidity through various mechanisms may inhibit the N2O flux. This may be related to the highest acidity of the media and the acidifying effects of fertilizer. As a recent study pointed out, the contributing microorganisms for N2O emissions may be more abundant than previously known . Especially, the tropical and boreal peat soils have a wide fungal diversity including denitrifiers. Peat moss as a soil amendment might be a potential source of fungal denitrifiers, which finally results in higher emission rates of N2O. In conclusion, the highest loss of NO3 – was obviously generated by the soil amendment application and plant transplantation. For as much as the blueberry is a perennial crop, this soil disturbance and heavy application of organic matter apply only in the establishment year. The subsequent years of plant management can be carried out without any deep tillage or organic amendment application that may release an excess amount of NO3. Taking into account the above mentioned characteristics of soil-plant-water-gas relations, the sawdust compost amended treatment has the least environmental impact in upland soil cultivation of blueberry. Over the past decade, the number of H-2A guest workers employed on California farms increased more than tenfold, so that almost 44,000 farm jobs were certified to be filled by H-2A workers in fiscal year 2022 . During FY2020, two-thirds of the H-2A jobs certified in California were in crop support services. Most crop support jobs were with farm labor contractors , but one sixth were hired directly by fruit producers. Almost 10% of the H-2A workers were hired directly by vegetable producers . Until the 2008–2009 recession, most H-2A workers were in southeastern states such as Florida.

However, the slowdown in migration of undocumented individuals after 2008–2009, combined with a stable demand for farm workers and the aging and settling of undocumented workers who arrived before 2008–2009, contributed to the rapid growth in the H-2A program in the three Pacific Coast states that employ half of U.S. farm workers, a third of whom work in California.This paper analyzes agricultural employment data from the California Employment Development Department and the Quarterly Census of Employment and Wages to understand changing patterns of farm worker employment in the 21st century. The data show that seasonality is declining in most regions and commodities, primarily because of higher employment during the winter months, which may reflect more winter pruning jobs and fewer summer harvesting jobs. Second, the data emphasize the increasing importance of non-farm crop support employers, mostly labor contractors, who bring workers to farms to perform specific tasks. More farms appear to be developing a year-round workforce that is hired directly and supplemented when needed with workers brought to farms by labor contractors, including H-2A guest workers . California requires all employers who pay $100 or more in wages to enroll in the state’s unemployment insurance system and pay taxes of 1.5% to 6.2% on the first $7,000 of each employee’s wages to cover the cost of unemployment benefits for laid-off workers . Employers also report their employment for the payroll period that includes the 12th of the month. Summing these monthly employment totals and dividing by 12 months generates average employment, also referred to as year-round equivalent jobs. The monthly employment measures allow us to determine the peak and trough employment months. Agricultural employment, as defined by the North American Industry Classification System , peaked at 470,000 in May 2020 and was 346,000 in March 2020, generating a peak-trough ratio of 1.4. More than 470,000 workers are employed on California farms sometime during the year. Workers who are employed only in payroll periods that do not include the 12th of the month, such as those who work only during the first, third, or fourth weeks of the month,flower buckets wholesale are excluded from average employment. In 2016, when California’s agricultural employment averaged 425,000, almost a million unique Social Security Numbers were reported by the state’s agricultural employers, suggesting 2.3 unique workers for each year-round equivalent job .California became the leading farm state in terms of sales in 1949, when Los Angeles County led the United States in farm sales . The state’s population doubled between 1950 and 1970, from 10 million to 20 million, and agricultural sales grew fastest in the San Joaquin Valley after water projects allowed more acres to be irrigated and suburbanization reduced the availability of farmland in coastal areas. Citrus and dairy farms in Southern California migrated north to SJV, while tree fruit farms moved from the urbanizing Bay Area to the San Joaquin and Sacramento valleys . Three SJV counties — Fresno, Kern and Tulare — accounted for 20% of California farm sales in 1949, a third in 2000, and almost half of the state’s farm sales in 2020 . Some crops that were already concentrated in the Sacramento and San Joaquin valleys expanded in acreage. For example, there were 90,000 bearing acres of almonds in 1950, almost 150,000 acres in 1970, 500,000 acres by 2000, and 1.3 million acres in 2022. Most of this additional almond acreage was in the San Joaquin Valley.

New orchards and dairies in the San Joaquin and Sacramento valleys were often larger and more efficient than the coastal farms they replaced, and their higher productivity was reflected in rising yields. Average yields of many fruits and vegetables doubled and tripled over the past three decades; bell peppers and cantaloupes are examples. Yield rose over 50% to 33 tons an acre for strawberries . The major change in California crop farming over the past half-century has been the rising share of high value fruits, nuts, vegetables, and melons, as well as horticultural specialties such as flowers and plants, in the state’s farm sales. In 1960, the value of fruit, vegetable, and horticultural commodities was two-thirds of the total value of California crops; since 2000, FVH commodities have accounted for over 90% of the value of California crops, reflecting growing consumer demand for fresh produce and nursery plants . Cotton was California’s most valuable crop in 1950; by 2000, cotton was the sixth most valuable crop, and by 2020 cotton was no longer among the state’s top 20 crops. The demand for FVH commodities rises with income, and rising farmland prices encouraged individuals and investors to buy farmland as a hedge against inflation in the 1970s, a decade in which the value of California farmland more than doubled . Higher interest rates in the 1980s led to a farm financial crisis that was more severe in mid-western states than in California, but encouraged some oil firms and conglomerates to sell their California farmland. The data in table 1 show that California’s farm sales almost tripled in three decades, and that fruit and nut sales almost quintupled. The value of the state’s vegetables and melons doubled, as did the value of greenhouse and nursery crops. The state’s farm sales were $17.8 billion in 1990, including $4.4 billion worth of fruits and nuts and $3.9 billion worth of vegetables. Farm sales were $27.2 billion in 2000, including $7.3 billion worth of fruits and nuts, $6.2 billion worth of vegetables, and $2.8 billion worth of greenhouse and nursery commodities. This rose to $37.5 billion in 2010, including $13.5 billion worth of fruits and nuts, $6.7 billion worth of vegetables, and $3.8 billion worth of greenhouse and nursery commodities. In 2020, farm sales were $49.1 billion, including $20.6 billion worth of fruits and nuts, $7.8 billion worth of vegetables, and $6.3 billion worth of greenhouse and nursery commodities. In real or inflation-adjusted terms, California farm sales rose by 40% over 30 years, and fruit and nut sales by 140%, while vegetable and nursery sales were little changed.Many FVH commodities are labor intensive, so expanding production increases the employment of farm workers. Rather than hiring workers directly, many farmers are turning to crop support service firms. These are non-farm businesses that bring workers to farms to accomplish specific tasks. For example, farmers may rely on labor contractors to bring crews of workers for a few weeks to prune, thin, or harvest their crops. Contractors may be the sole employers of the workers they bring to farms under some labor laws, such as unemployment insurance and workers’ compensation, and joint employers with farms under others, such as the Agricultural Labor Relations Act. Over the past three decades, California farmers hired 20% fewer workers directly, reducing average direct-hire employment in crops from 203,000 to 160,000. Meanwhile, crop-support employment rose by 60%, from an average of 132,000 in 1990 to 212,000 in 2020. Combined crop and crop-support employment accounts for over 90% of California’s agricultural employment. Within crop support employment,the farm labor contractor share of average crop-support employment rose from 60% to 67% . FVH commodities account for 90% of direct-hire crop employment, including 55% for fruits and nuts, 20% for vegetables and melons, and 15% for greenhouses and nurseries.